MR Breast Cancer

Hall B                        Monday 14:00-16:00                                                                           Computer 103           

14:00         4741.     Shutter-Speed Model Dynamic Contrast-Enhanced MRI to Reduce Unnecessary Surgeries of Atypical Breast Lesions: A Preliminary Study

Luminita Alina Tudorica1, Stephanie Hemmingson1, Karen Oh1, Arpana Naik1, Sunitha Thakur2, Elizabeth A. Morris2, Mark Kettler1, Ian J. Tagge1, Jason A. Koutcher2, Charles S. Springer1, Wei Huang1

1Oregon Health & Science University, Portland, OR, United States; 2Memorial Sloan Kettering Cancer Center, New York, NY, United States

Three of 28 core needle biopsy-proven high-risk atypical breast lesions were upgraded to malignancies following surgical excisions as standard care.  Correlations with pre-biopsy quantitative DCE-MRI results show that the Shutter-Speed Model (SSM) analyses of DCE-MRI data discriminate the atypical lesions between those completely benign and those containing malignancies with high accuracy.  SSM DCE-MRI can potentially be used to reduce unnecessary surgeries of atypical lesions.

14:30         4742.     Characterizing Suspicious Lesions with MR Guided Diffuse Optical Breast Imaging

Colin Morehouse Carpenter1,2, Shudong Jiang2, Steven P. Poplack3, Roberta M. diFlorio-Alexander3, Brian William Pogue2, Keith David Paulsen2

1Radiation Oncology, Stanford University School of Medicine, Stanford, CA, United States; 2Thayer School of Engineering at Dartmouth, Hanover, NH, United States; 3Radiology, Dartmouth Hitchcock Medical Center, Lebanon, NH, United States

Breast MR has high sensitivity, yet suffers from comparatively low specificity.  Optical imaging may aid MR mammography by providing spatial maps of disease-specific tissue properties such as total hemoglobin, oxygen saturation, water content, and tissue microstructure scatter, which have been shown in several studies to offer high specificity to malignant cancer.  A multimodality MR-guided optical breast imaging instrument (MRg-OBI) has been developed and validated through numerous phantom and healthy volunteer studies.  This study examined the ability of MRg-OBI in characterizing malignant from benign lesions in five patients. The results show that total hemoglobin is a good indicator of malignancy, with tumor to background contrast varying greatly from 1.25 up to 8.0, compared to less than 1 for the benign/fully responded lesions.

15:00         4743.     Associations Between MR Derived Vascular, Shape and Texture Parameters with Histological Descriptors

Martin D. Pickles1, Peter Gibbs1, Martin Lowry1, Lindsay W. Turnbull1

1Centre for MR Investigations, University of Hull, Hull, East Yorkshire, United Kingdom

Features such as shape (round, irregular), enhancement (homogeneous, heterogeneous), and kinetic curve assessment (persistent, plateau and washout) have been used to aid in the classification of breast lesions. These features may also help to highlight patients who subsequently have a reduced overall and disease free survival intervals. The aim of this work was to determine if there were any associations between pre-treatment MR derived quantitative descriptors (shape, enhancement and kinetic curve assessment) and traditional prognostic indicators. This work has demonstrated that when comparing traditional prognostic indicators (nodal ± hormonal status) significant differences in shape, texture and vascular kinetics are apparent.

15:30         4744.     Evaluation of Sentinel Node with High Resolution Magic Angle Proton Magnetic Resonance Spectroscopy in Breast Cancer Patients: A Pilot Study

Surender Kumar1, Raja Roy2, Sandeep Kumar, Madhumati Goel, Ankita Rathore

1General Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India; 2CBMR, Centre of Biomedical Magnetic Resonance, Lucknow, Uttar Pradesh, India

The extent of axillary lymph node involvement in patients with cancer breast is an important prognostic marker. Prophylactic axillary dissection is associated with significant morbidity in clinically negative axilla. The intra-operative sentinel node biopsy (SNB) provides a basis for omitting the routine axillary dissection. However, it has limited sensitivity and requires complicated training and infrastructure. We report the use of high resolution magic angle proton magnetic resonance spectroscopy (HRMAS) in assessing the axillary nodal status with increased sensitivity.

                                   Tuesday 13:30-15:30                                                                          Computer 103           

13:30         4745.     Magnetization Transfer Imaging of Breast Cancer at 3T

Sungheon Kim1, Anne Zeleniuch-Jacquotte2, Malcolm C. Pike3, Silvia Formenti4, Linda Moy1

1Center for Biomedical Imaging, Radiology, NYU School of Medicine, New York, NY, United States; 2Environmental Medicine, NYU School of Medicine, New York, NY, United States; 3Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA, United States; 4Radiation Oncology, NYU School of Medicine, New York, NY, United States

This study was to investigate the feasibility of using MTR to differentiate breast tissues with the patients undergoing diagnostic MRI scans at 3T. The MTR of muscle (41.8 ˇľ 8.1 %) was significantly (p < 0.01) higher than that of fibroglandular tissue (33.1 ˇľ 5.6 %). The MTR of fibroglandular tissue was significantly (p < 0.01) higher than that of FCC (23.6 ˇľ 3.4 %). The difference in MTR between FCC and tumor (20.1 ˇľ 4.2 %) was marginally significant (p=0.04). In addition, MT images were able to accentuate the signal differences in normal structures in the breasts.

14:00         4746.     The Role of Magnetisation Transfer Imaging in the Differentiation of Malignant and Benign Tissues

R. G. Sah1, U. Sharma1, R. Prashad2, N. R. Jagannathan1

1Departmet of NMR and MRI facility, All India Institute of Medical Sciences, New Delhi, India; 2Departmet of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India

This study evaluates the potential role of magnetization transfer imaging (MTI) in the differentiation of malignant and benign breast lesions at 1.5 T. The MT ratio was determined in 72 women; 57 locally advanced breast cancer patients (mean age, 43.8 ± 9.0); 10 benign breast cases (mean age, 28.3 ± 9.5) and 5 normal volunteers (mean age, 37.8 ± 15.4). The mean MTR of malignant lesions was statistically significantly higher (p=0.01) compared to the benign lesions and the fibroglandular tissues of normal volunteers suggesting the possible utility of MT imaging in the differentiation of various breast tissues.

14:30         4747.     Metabolomic Analysis of Human Breast Cancer - not available

Leo L. Cheng1, Elita DeFeo, Yannick Berker, Elena Brachtel

1Radiology/Pathology, Massachusetts General Hospital, Charlestown, MA, United States

Research and technology has lead to an increase of early breast cancer detections, however there are still some controversies involving disease management.  Traditional mastectomy followed by chemotherapy and radiotherapy is no longer standard protocol.  Using HRMAS we have shown that metabolomic spectra from various pathological features can provide enough information to distinguish between cancerous vs. benign tissue, and tumor type and grade.  We hope to use these findings to design new MRS paradigms aimed at non-invasive diagnosis, characterization and monitoring of breast tumors that will optimize patient survival and comfort, while reducing healthcare costs.

15:00         4748.     Effects of Temporal Resolution on Breast Cancer Diagnostic Accuracy by Quantitative Dynamic Contrast-Enhanced MRI

Ian J. Tagge1, Xin Li1, Luminita Alina Tudorica1, Yiyi Chen1, Stephanie Hemmingson1, Elizabeth A. Morris2, Charles S. Springer1, Wei Huang1

1Oregon Health & Science University, Portland, OR, United States; 2Memorial Sloan Kettering Cancer Center, New York, NY, United States

High temporal-resolution research DCE-MRI data from 66 suspicious breast lesions were resampled to mimic typical clinical protocols with low temporal-resolution.  The Standard Model (SM) and Shutter-Speed Model (SSM) pharmacokinetic analyses show that both Ktrans and ¦¤Ktrans [ˇÔ Ktrans(SSM) ¨C Ktrans(SM)] are significantly underestimated at the lower temporal resolution, and the diagnostic accuracies of both parameters are considerably compromised.

                                   Wednesday 13:30-15:00                                                                     Computer 103           

13:30         4749.     Fat Water Ratio and Diffusion-Weighted MRI Applied to the Measure of Breast Density as a Cancer Risk Biomarker - not available

Ted Trouard1,2, Patricia Thompson3, Chuan Huang4, Maria Altbach2, Matthew Kupinski2, Denise Roe3, Kimberly Fitzpatrick2, Per Granstrom2, Georgette Frey3, Scott Squire2, Veronique Poulin3, Alison Stopeck3

1Biomedical Engineering, University of Arizona, Tucson, AZ, United States; 2Radiology, University of Arizona, Tucson, AZ, United States; 3Arizona Cancer Center, University of Arizona; 4Mathematics, University of Arizona

Breast density, as measured by mammography, is associated with elevated risk of breast cancer.  Decreases in mammographic breast density have also been linked with beneficial effects of chemoprevention.  However, the low precision and reproducibility of mammography, as well as exposure to ionizing radiation, limits the use of mammographic breast density as a biomarker for risk and prevention.  In this study we have employed Fat Water Ratio (FWR) MRI for assessment of breast density and compared the results to conventional mammography and to apparent diffusion coefficients (ADCs) measured by diffusion-weighted (DW) MRI.

14:00         4750.     Possible Prognostic Value of Contralateral Normal Breast Enhancements in DCE-MRI of Breast Cancer Patients Undergoing Chemotherapy

Hon Yu1, Jack Hsu1, Ke Nie1, Muqing Lin1, Siwa Chan2, Jeon-Hor Chen1,2, Rita S. Mehta3, Orhan Nalcioglu1, Min-Ying Lydia Su1

1Center for Functional Onco-Imaging, University of California, Irvine, CA, United States; 2Department of Radiology, China Medical University Hospital, Taichung, Taiwan; 3Department of Medicine, University of California, Irvine, CA, United States

The suggested association between the chemotherapy-induced ovarian suppression and a positive prognostic impact for more favorable treatment outcome in pre-menopausal women with breast cancer was investigated. Using the enhancement values of DCE-MRI measured from the fibroglandular tissue of contralateral normal breast as a measure of ovarian suppression effect, our retrospective study indicates a possible prognostic value of such measurement via an association between an early onset of chemotherapy-induced ovarian suppression and positive treatment outcomes among the younger group of women (< 55 yr.). The observed association between early onset of reduced perfusion and poor treatment outcome among the older group of women (ˇÝ 55 yr.) may represent an additional potential of the prognostic value in treatment-induced effects measured from the normal breast.

14:30         4751.     MR Spectroscopy of Breast Cancer Patients for Prediction of Treatment Response – Combining in Vivo and Ex Vivo Analysis

Beathe Sitter1, Mariann Gjervik Heldahl1, Tone Frost Bathen1, Anna Bofin2, Steinar Lundgren1,3, Ingrid Susann Gribbestad1

1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway; 3Department of Oncology, St. Olavs University Hospital

In vivo and ex vivo 1H MR spectroscopic data were obtained prior to treatment from 19 patients assigned to neoadjuvant chemotherapy. Comparing findings obtained in vivo and ex vivo showed that concentrations of total choline (tCho) determined by ex vivo MRS were significantly higher in tissue from patients with detectable tCho by in vivo MRS compared to those without detectable choline by in vivo MRS. We also found that patients with complete response to treatment had significantly higher levels of GPC (p=0,037) than patients not having complete response.

                                   Thursday 13:30-15:30                                                                        Computer 103           

13:30         4752.     Role of Choline as a Biomarker of Cell Proliferation to Differentiate HER2/neu Positive and Negative Breast Cancers Patients

Naranamangalam R. Jagannathan1, Rani G. Sah1, Uma Sharma1, Rajinder Parshad2

1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India; 2Department of Surgery, All India Institute of Medical Sciences, New Delhi, Delhi, India

The choline concentration and tumor volume were determined using in-vivo MRS and MRI in 53 invasive ductal carcinoma patients at 1.5 T with known HER2/neu status. The tCho concentration for HER2/neu positive cases was 4.8 ± 3.3 mmol/kg which was statistically significantly higher compared to HER2/neu negative cases (2.7 ± 0.7 mmol/kg; p=0.007). However, the tumor volume for the Her2/neu positive cases (47.9±56.1) and negative cases (45.6±48.3) were similar (p=0.84). The increase in tCho concentration observed in Her2/neu positive patients may be attributed to the high proliferative activity of the Her2neu positive tumors.

14:00         4753.     Choline as a Biomarker a Better Predictor of Early Response of Breast Cancer Than Tumor Volume? Sequential Study of the Therapeutic Response of Locally Advanced Breast Cancer Patients Undergoing Neo-Adjuvant Chemotherapy (NACT)

R. G. Sah1, U. Sharma1, R. Prashad2, N. R. Jagannathan1

1Departmet of NMR and MRI facility, All India Institute of Medical Sciences, New Delhi, India; 2Departmet of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India

We report here that tCho concentration as a useful biomarker for early prediction of tumor response compared to tumor volume. tCho and volume were calculated in  30 locally advanced breast cancer patients undergoing NACT using MRS and MRI. In clinical responders, pre-therapy tCho was 5.1 (0.48) mmol/kg which significantly decreased to 2.6 (0.51) after I NACT and showed gradual decrease thereafter, while volume showed significant decrease only after II NACT. Reduction in tCho and tumor volume after I NACT was 39.8% and 6.5% respectively in responders. Non-responders showed an increase of tCho by 52.9% and 7% reduction in volume.

14:30         4754.     Correlation Between Estrogen Receptor Positive (ER+) and Estrogen Receptor Negative (ER-) Status with TCho Concentration and Tumor Volume in Breast Cancer Patients.

Naranamangalam R. Jagannathan1, Rani G. Sah1, Uma Sharma1, Rajinder Parshad2

1Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, Delhi, India; 2Department of Surgery, All India Institute of Medical Sciences, New Delhi, Delhi, India

The tCho concentration and tumor volume were calculated using in-vivo MRS and MRI in estrogen positive and negative patients (n=46) with confirmed invasive ductal carcinoma at 1.5 T. The tumor volume for the estrogen positive patients was (33.57 ± 45.7) significantly higher (p=0.03) compared to estrogen negative patients (67.2 ± 60.8). However, the tCho concentration was similar in estrogen positive (4.2 ± 2.3 mmol/kg) and estrogen negative patients (4.1 ± 3.5) mmol/kg. The increase in the tumor volume may be attributed to the higher microvessels density in ER negative cancer patients.

15:00         4755.     SER Volume Predicts Malignancy in DCE MRI-Detected Secondary Occult Breast Lesions

Vignesh Arasu1, Ryan Cheng-Ying Chen1, David Caryl Newitt1, Belinda Chang1, Hilda Tso1, Nola M. Hylton1, Bonnie Nancy Joe1

1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States

Breast MRI, although sensitive for identifying cancer extent, has been criticized for its poor specificity in staging preoperative patients, leading to unnecessary biopsies and changes in surgical management.  Signal enhancement ratio (SER) of contrast-enhanced breast MRI lesions characterizes neoangiogenesis in cancer, with high values predicting malignancy. We investigated if SER also predicts malignancy in new lesions found secondary to the known primary cancer when staging preoperative patients. Our results show that high total tumor SER volume, washout SER volume, and high peak SER significantly predict secondary malignant lesions. These results potentially improve the efficacy of preoperative MRI for surgical management.

Pelvic Cancers (Clinical Studies)

Hall B                        Monday 14:00-16:00                                                                           Computer 104           

14:00         4756.     Impact of T1 Estimate Variation on DCE-MRI Derived Pharmacokinetic Values in Rectal Tumours

Moreno Pasin1,2, Gloria Castellazzi1, Paul Summers2, Roberto Di Filippi2, Luke Bonello2, Giuseppe Petralia2, Massimo Bellomi2

1Struttura Complessa di Radiologia/Diagnostica per immagini, Istituto Neurologico IRCCS- Fondazione Casimiro Mondino, Pavia, Lombardia, Italy; 2Radiology, Istituto Europeo di Oncologia, Milan, Lombardia, Italy

Variability in two-point T1 estimation may lead to uncertainty in derived DCE parameters. We examined the impact of T1 estimate noise on Ktrans, Kep, Ve, using two, low flip angle scans combined with a single dynamic DCE measurement and ROI definition in 9 rectal adrenocarcinoma patients at pre- and post- neoadjuvant treatment examinations. Ktrans and Ve variations attributable to T1 estimates were less than 5%, though variability in Ve may be exaggerated by peristaltic motion. The variation in Kep was not value dependent. We recommend the use of an aniperistaltic agent for rectal DCE to reduce variation in Ve.

14:30         4757.     Initial Observations from Multimodal Imaging Assessment of Rectal Tumors with Dynamic Contrast Enhanced and Diffusion Weighted Magnetic Resonance Imaging, Perfusion Computed Tomography and Positron Emission Tomography.

Giuseppe Petralia1, Paul Summers1, Luke Bonello1, Stefano Viotti1, Roberto Di Filippi1, Laura Traviani2, Maria Giulia Zampino3, Dow-Mu Koh4, Maria Cristina Leonardi5, Antonio Chiappa6, Massimo Bellomi1

1Radiology, Istituto Europeo di Oncologia, Milan, Lombardia, Italy; 2Nuclear Medicine, Istituto Europeo di Oncologia, Milano, Italy; 3Medical Care Unit, Department of Medicine, Istituto Europeo di Oncologia, Milan, Lombardia, Italy; 4Radiology, Royal Marsden Hospital, Sutton, United Kingdom; 5Radiotherapy, Istituto Europeo di Oncologia, Milan, Lombardia, Italy; 6General and Laparoscopic Surgery, Istituto Europeo di Oncologia, Milan, Lombardia, Italy

Functional imaging techniques have potential in monitoring neoadjuvant chemoradiation therapy and predicting therapy outcome in locally advanced rectal cancers. We compared four different functional modalities (DCE-MR, DW-MR,CTp and PET) in patients with locally advanced rectal cancer who underwent imaging with all modalities before and after neoadjuvant treatment. From our small patient population we observed a correlation between Kep and PS, both estimates of capillary permeability (R=0.93), and a trend to correlation between Ktrans and PS (R= 0.47), whereas negative correlations were observed between Ktrans and SUV (R=-0.78), Ve and SUV (R=-0.86), and a negative trend for ADC and SUV (R=-0.50).

15:00         4758.     Quantitative Analysis of Indexes from DWI and PET/CT in Primary Rectal Cancer

Jing Gu1, Pek-lan Khong1, Silun Wang1, Queenie Chan2, Wailun LAW3, Rico Kingyin Liu3, Jingbo Zhang1

1Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong; 2Philips Healthcare, Philips Electronics Hong Kong Limited, Hong Kong, Hong Kong; 3Division of Colorectal Surgery, The University of Hong Kong, Hong Kong, Hong Kong

We aim to assess the correlations between parameters apparent diffusion coefficient (ADC) measured by DWI and standardized uptake value (SUV) measured by 18F-FDG PET in rectal caner. Significant negative correlations were found between ADC and SUV in primary rectal adenocarcinomas. ADC may thus have the potential as a useful biomarker in oncologic imaging.

15:30         4759.     Dynamic Contrast-Enhanced MRI of Primary Rectal Cancer at 3T: Correlation with Positron Emission Tomography

Jing Gu1, Pek-lan Khong1, Silun Wang1, Queenie Chan2, Wailun LAW3, Rico Kingyin Liu3, Jingbo Zhang1

1Diagnostic Radiology, The University of Hong Kong, Hong Kong, Hong Kong; 2Philips Healthcare, Philips Electronics Hong Kong Limited, Hong Kong, Hong Kong; 3Division of Colorectal Surgery, The University of Hong Kong, Hong Kong, Hong Kong

We aim to assess the correlations between parameters measured on DCE-MRI and 18F-FDG PET in rectal cancer. We found positive correlations between kep measured by DCE-MRI and SUV values measured by PET/CT. Our findings may indicate that kep during contrast washout phase is better associated with tumor metabolism than Ktrans which is influenced by multiple factors during contrast uptake phase. kep may have the potential as a useful biomarker to reflect biological characteristics of rectum cancer

                                   Tuesday 13:30-15:30                                                                          Computer 104           

13:30         4760.     Functional Imaging of Peritoneal Disease in Ovarian Cancer: Changes in Apparent Diffusion Coefficients Predict Biochemical Response to Chemotherapy

Stavroula Kyriazi1,2, David J. Collins1, Veronica A. Morgan2, Catherine J. Simpkin2, Nandita M. deSouza1,2

1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2Royal Marsden Hospital NHS Foundation Trust, Sutton, Surrey, United Kingdom

Biochemical (Ca125) monitoring of chemotherapeutic efficacy in advanced ovarian cancer has limited sensitivity early in the course of treatment. Diffusion-Weighted Imaging of peritoneal disease improves anatomical delineation but its role in quantification of treatment response has not been established. This study explores the value of Apparent Diffusion Coefficients calculated for the entire metastatic tumour burden in identifying biochemical response to platinum-based chemotherapy. Although pretreatment ADC values were not predictive, an ADC increase after the first cycle of treatment was highly indicative of chemosensitivity. ROC analysis for %ADC change after the first cycle yielded an area under curve AUC=0.933. These findings may facilitate individualised treatment strategies in advanced ovarian cancer.

14:00         4761.     Diffusion-Weighted Imaging of Uterine Endometrial Cancer Using the Apparent Diffusion Coefficient Value at 3.0 T MRI: Differentiation Endometrial Cancer from Normal Endometrium and Endometrial Benign Lesions

Takuro Kamiyama1, Yoshihiko Fukukura2, Koji Takumi2, Toshikazu Shindo2, Yuichi Kumagae2, Akihiro Tateyama2, Takahiro Tsuji3, Tsutomu Douchi3, Masayuki Nakajo2

1Department of Radiology, National Hospital Organization Kagoshima Medical Center, 8-1 Shiroyama-cho, Kagoshima City, Kagoshima, Japan; 2Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, Japan; 3Department of Reproductive Pathophysiology and Obstetrics-Gynecology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, Kagoshima, Japan

Uterine endometrial cancer is the most common gynecological malignancy. The development of MR scanner with high field strength resulted in improvement in diffusion-weighted (DW) imaging. Apparent diffusion coefficient value of the tissue which is derived from DW imaging has been known to characterize malignant or benign lesions. The goal of this study is to evaluate the feasibility of DW imaging at 3T MRI for uterine endometrial cancer. The results of our study suggest that DW imaging of uterine endometrial lesions is feasible in differentiating endometrial cancer from normal endometrium and endometrial benign lesions such as endometrial hyperplasia and polyps.

14:30         4762.     Increasing Registration Accuracy by Sub-Volume Based Mutual Information Registration

Joakim Jonsson1, Mikael Karlsson1, Magnus G. Karlsson2, Tufve Nyholm2

1Department of Radiation Sciences, Radiation Physics, Umeĺ University, Umeĺ, Sweden; 2Department of Radiation Physics, Umeĺ University Hospital, Umeĺ, Sweden

In many cases where an organ of interest is free to move within the patient anatomy, e.g. the prostate gland, normal image registration techniques are insufficient. The patient external contour and bony anatomy will heavily influence the registration, causing the actual organ of interest to be misaligned. In order to overcome this problem, the registration can be performed in such a way that the information available in the organ of interest and regions in close proximity to it is more important to the registration algorithm. This study evaluates the accuracy of such a sub-volume based approach.

15:00         4763.     Effect of Field Strength and Peripheral Zone Fraction on T2 from Tumor and Non-Tumor Prostate Regions

Sophie F. Riches1, Veronica A. Morgan2, Sharon Giles2, Catherine Simpkin2, Nandita deSouza1

1Cancer Research UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research & Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom; 2Cancer Research UK and EPSRC Cancer Imaging Centre, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom

Tumor detection within the prostate depends on T2-weighted contrast. This study compares T2 values at 3T and 1.5T and investigates differences in T2 contrast with fractional volume of the peripheral zone (PZ). T2 values obtained at 3T were not significantly different  to those at 1.5T for any prostate region. Patients with a low PZ  to whole prostate volume showed significantly reduced T2 in PZ compared to those with larger PZ fractions.  In patients with low fractional PZ volume, therefore, T2 values of PZ may be indistinguishable from tumor, reducing the ability to detect tumor within the PZ in these patients.

                                   Wednesday 13:30-15:30                                                                     Computer 104           

13:30         4764.     A New Harvesting Method to Provide High Quality Prostate Cancer Tissue Suitable for 1H HR MAS MR Spectroscopy and Gene Expression.

Helena Bertilsson1,2, May-Britt Tessem3, Ingrid Gribbestad4, Haakon Skogseth1, Trond Viset5, Anders Angelsen, 2,6, Jostein Halgunset1

1Dept. of Laboratory Medicine and Children's and Women's Health, NTNU, Trondheim, Norway; 2Dept. of Urology, St Olav University Hospital, Trondheim, Norway; 3Dept. of Circulation and Medical Imaging , Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 4Dept. of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 5Dept. of Pathology and Medical Genetics, St Olav University Hospital, Trondheim, Norway; 6Dept. of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway

New research on the genetic and metabolic level of prostate cancer is important for future disease management in diagnostics, choice of treatment and prognosis. This study describes a highly standardized method for snap-freezing of a whole prostate slice that is safe (without interfering with the routine diagnostics), easy to practise, and results in tissue with highly intact molecular content suitable for ex vivo MR spectroscopy and gene expression of the same sample. The present harvesting method is applicable to all prostate cancer patients and stores the snap-frozen tissue without fixatives, leaving it available for all kinds of future research technologies.

14:00         4765.     Volumetric Reconstruction with Superimposed MRS Metabolic Map for the Assessment of Prostate Cancer

Angel Alberich-Bayarri1, Luis Marti-Bonmati1,2, Roberto Sanz-Requena1, Javier Sánchez-González3, Gracián García-Martí1, Rosario Pérez1

1Radiology, Quiron Valencia Hospital, Valencia, Spain; 2Radiology, Dr. Peset University Hospital, Valencia, Spain; 3Clinical Science, Philips Healthcare, Madrid, Spain

The diagnosis and accurate localization of prostatic carcinoma by 3D multivoxel MR spectroscopy (MRS) analysis is often complicated on a slice-by-slice basis. A semi-automated individualized method was developed to obtain a 3D reconstruction of the prostate with superimposition of metabolic results for an intuitive depiction and rapid localization of the suspicious malignant zones. The (Cho+Cr)/Cit ratio was calculated in a voxel-by-voxel basis and used as a metabolic index to be combined with the 3D reconstructions of the prostate.

14:30         4766.     Comparison of Look-Locker and Variable Flip Angle T1 Mapping for DCE-MRI in Prostate Patients at 3T

Wei Liu1,2, Baris Turkbey2, Julien Senegas3, Stefanie Remmele3, Christian Stehning3, Dagane Daar4, Yuxi Pang5, Marcelino Bernardo4, Peter Choyke2

1Clinical Sites Research Program, Philips Research North America, Briarcliff Manor, NY, United States; 2Molecular Imaging Program, National Cancer Institute, Bethesda, MD, United States; 3Sector of Tomographic Imaging, Philips Research Europe, Hamburg, Germany; 4Molecular Imaging Program, National Cancer Institute, SAIC-Frederick Inc., Bethesda, MD, United States; 5Philips Healthcare, Cleveland, OH, United States

T1 maps from variable flip angle (VFA) approach were compared with Look-Locker T1 maps to investigate the accuracy of the VFA T1 mapping in prostate cancer patients. Despite larger variations and lower SNR, VFA T1 mapping demonstrated a good correlation with the Look-Locker technique for prostate T1. Pharmacokinetic parameters based on VFA and Look-Locker T1 maps demonstrated similar performance in differentiation of tumor tissues. Our results suggest that with actual flip angle correction and slice oversampling to suppress inflow, VFA approach can generate satisfactory T1 maps for DCE MRI in patients undergoing MRI for prostate cancer.

15:00         4767.     DCE-MRI for the Detection of Patients with Recurrent Prostate Cancer After Radiotherapy; a Matched Case-Control Study.

Maaike R. Moman1, Greetje Groenendaal1, Marco van Vulpen1, Gijsbert H. Bol1, Uulke A. van der Heide1

1Radiotherapy, University Medical Center Utrecht, Utrecht, Netherlands

The interpretation of DCE-MRI of the prostate can be difficult after radiotherapy, because of changes in microvasculature. This study demonstrates that DCE-MRI shows differences between patients with recurrent prostate cancer after radiotherapy, compared to matched control patients. These differences can be utilized for the detection of patients with recurrent prostate cancer in the follow-up after treatment.

                                   Thursday 13:30-15:30                                                                        Computer 104           

13:30         4768.     Dynamic Contrast Enhanced MRI Post-Prostatectomy for a Rising PSA: Implications for Radiotherapy

Radka Stoyanova1, Raj Rajpara1, Elizabeth Bossart1, Victor Casillas2, Jill Palma1, May Abdel-Wahab1, Alan Pollack1

1Radiation Oncology, University of Miami, Miami, FL, United States; 2Diagnostic Radiology, University of Miami, Miami, FL, United States

We present analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for identification of local recurrence of prostate cancer in men who underwent radical prostatectomy and had a subsequent rising Prostate-Specific Antigen (PSA). Our results indicate that we can detect abnormalities suggestive of residual tumor in the prostate bed in nearly 75% of patients evaluated for radiation therapy (RT). Because patients treated with salvage RT often develop a rising PSA later and there is some evidence for a RT dose response, targeting of the contrast-enhancing areas specifically may improve tumor control and limit toxicity.

14:00         4769.     Effect of External Beam Radiotherapy on Prostate ADC Values

Daniel Wilson1, Sarah Bacon1, Brendan Carey2

1Medical Physics, Leeds Teaching Hospitals NHS Trust, Leeds, West Yorkshire, United Kingdom; 2Radiology, Leeds Teaching Hospitals NHS Trust, Leeds, West Yorkshire, United Kingdom

Prostate ADC values were calculated using a variety of b-value combinations from b=0, 50, 300 and 500 s/mm2. The calculated ADC depended on the combination of b-values used. All combinations showed a decrease in ADC post radiotherapy compared to pre radiotherapy. This difference was statistically significant for all combinations except b=300 and 500 s/mm2 combined. This decrease in ADC may be a result of radiation induced cellular changes.

14:30         4770.     Prostate MRS in the Presence of Gold Seed Fiducial Markers

Ralph Noeske1, Beat Werner2, Charlie Ma3, Murshed Hossain3, Mark Buyyounouski3, Timo Schirmer4

1Applied Science Laboratory, GE Healthcare, Potsdam, Germany; 2Kinderspital Zurich, Switzerland; 3Fox Chase Cancer Center, Philadelphia, PA, United States; 4Applied Science Laboratory, GE Healthcare, Germany

MR Spectroscopy (MRS) has great potential for guiding radiotherapy of prostate cancer by identifying bulky and/or high grade tumors suitable for dose escalation. However, image guided therapy typically employs permanently implanted gold seed fiducial markers (GSFM) which aid in daily prostate localization prior to treatment. The impact of GSFM on the quality of MRS is unknown. This phantom study presents the potential impact of GSFM on the quality of 1H MRS data. Signal drops in the vicinity of GSFM up to 47% were observed. Further investigation will show if advanced processing tools allow evaluation of areas with larger signal drops.

15:00         4771.     MRI Method Developments for Stand-Alone MRI and CT Fiducial-Based Registration

Warren Foltz1, Vickie Kong1, Siddharta Baxi1, Varadarajan Kumar1, Peter Chung1, David Jaffray1, Cynthia Ménard1

1Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, Canada

MRI and CT fiducial-based registration for prostate radiation therapy requires MR images which clearly display both  implanted gold fiducial markers and the prostate boundary.  However, stand-alone acquisitions of standard diagnostic techniques do no accomplish both of these tasks reliably at 1.5 Tesla.  Consequently, fiducial-sensitive images and anatomical images for contouring are acquired in separate acquisitions, which increases protocol duration and compromises the registration process to prostate motion.  This abstract introduces strategies which provide T2 or T2-like contrast for contouring, yet provide a moderate amplification of gold fiducial markers, utilizing the frequency response of ssfp and the off-resonance blur function of spiral imaging.  A preliminary experiment validated an inconsistent visualization of gold 'seeds' in standard diagnostic T2-weighted images via retrospective review.  A second experiment demonstrated that spiral and ssfp strategies provide consistent fiducial visibility with an adequate contrast for contouring.

Prostate Cancer

Hall B                        Monday 14:00-16:00                                                                           Computer 105           

14:00         4772.     Assesing Prostate Cancer Growth with Intact Tissue MRS and MRNA of Spermine Anabolic Enzymes - not available

Leo L. Cheng1, David Kaul2, Chin-Lee Wu3, Christen Adkins, Kate Jordan, Piet Habbel4, Randall Peterson5, W. Scott McDougal, Ute Pohl

1Radiology/Pathology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, United States; 2Pathology/ Center for Anatomy, Institute of Cell Biology and Neurobiology, Massachusetts General Hospital/Charite - Universitatsmedizin; 3Pathology/Urology, Massachusetts General Hospital; 4Center for Anatomy, Institute of Cell Biology and Neurobiology, Charite - Universitatsmedizin; 5Medicine, Massachusetts General Hospital

The inability of current pathology to distinguish between a latent form of prostate cancer and a fast growing tumor necessitates new assays that can determine tumor biological activity.  We measured concentrations of spermine, an endogenous PCa growth inhibitor, from prostatectomy tissue with HRMAS 1HMRS, and quantified the expression levels of mRNA for enzymes in the spermine synthesis and degradation pathways for different pathological features.  Our findings suggest the presence of PCa activates spermine production, which delays PCa progression.  These enzyme related mRNA results could potentially be implemented in the clinic, allowing patients to make a more informed decision about treatment.

14:30         4773.     Automated Quality Control of Prostate Cancer MRSI Using Independent Component Analysis

Alan James Wright1, Thiele Kobus1, Thomas Hambrock1, Tom W. Scheenen1, Arend Heerschap1

1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Magnetic Resonance Spectroscopic Imaging (MRSI) of prostate cancer patients can provide information on the detection and localization of prostate cancers. Automatic processing of MRSI data requires an automated quality control step. We present a method for quality control of 3T MRSI data from prostate cancer patients that separates raw spectral data as voxels of acceptable and unacceptable quality. This is done with a feature extraction method based on independent component analysis. The separation achieved is comparable to the gold standard of expert decision.

15:00         4774.     Rapid 5-Minute Echo-Planar Spectroscopic Imaging of Prostate Cancer Patients at 3T

Galen Durant Reed1,2, Peder E. Larson1, John Kurhanewicz1,2, Daniel B. Vigneron1,2

1Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States; 2Joint Graduate Group in Bioengineering, UCB / UCSF, Berkeley, CA, United States

The long acquisition times for the 3D phase encoding traditionally employed in proton magnetic resonance spectroscopic imaging (MRSI) of the prostate can be prohibitively long. A 3T MRSI sequence with a flyback echo-planar readout recently developed and clinically implemented at UCSF shows greatly reduced scan times. This time reduction allows for larger acquisition matrices and longer repetition times to avoid metabolite saturation. Comparison with a 1.5T 3D phase-encoded sequence showed that the flyback sequence can achieve comparable spatial resolution, improved spectral resolution, and significantly improved SNR in a shorter scan time.

15:30         4775.     Diagnostic Performance of 1.5 Tesla Endorectal MR Imaging and MR Spectroscopic Imaging for the Detection of Locally Recurrent Prostate Cancer After External Beam Radiation Therapy

Antonio Westphalen1, Fergus V. Coakley, Vivian Weinberg, Mack Roach III, Jane Z. Wang, John Kurhanewicz

1University of California, San Francisco, San Francisco, CA, United States

The addition of MR spectroscopic imaging to T2-weighted MR imaging significantly improves the detection of locally recurrent prostate cancer after definitive external beam radiotherapy. The resulting information may assist the clinician to advise patients about subsequent clinical evaluation, selecting those for whom targeted hemi-prostate biopsy is appropriate to confirm disease. Although targeted therapies may be offered to patients in whom very minimal recurrent disease is diagnosed, hemi-prostate imaging evaluation is sufficiently accurate to obviate the need for sextant localization, since the most commonly recommended salvage treatments (radical retropubic prostatectomy and permanent LDR brachytherapy) treat the entire gland.

                                   Tuesday 13:30-15:30                                                                          Computer 105           

13:30         4776.     Differentiation Between Malignant and Benign Prostatic Diseases: Evaluated by MR Diffusion Tensor Imaging at 3.0T

Saying Li1, Chunmei Li1, Min Chen1, Xuna Zhao2, Cheng Zhou1

1Radiology, Beijing Hospital, Beijing, China; 2Philips Medical System, China, China

To investigate the characteristcs of DTI at 3.0T in differentiating prostate cancer and benign prostatic diseases. DTI was performed in 30 patients with prostate cancer, prostatitis and /or BPH , and in 20 healthy volunteers. Decreased ADC and increased FA values were found in the central gland , compared with the peripheral zone. We also observed reduced ADC and higer FA values in cancer. The sensitivity and specificity of two values for differentiating prostate cancer and benign diseases were 94.4%, 70.3% and 81.1%, 66.7% respectively. In conclusion, DTI may be a potential tool in differential diagnosis of prostatic diseases.

14:00         4777.     Prostate Cancer : Are There Differences Between Native Diffusion-Weighted Images and the Apparent Diffusion Coefficient Map in Tumor Detection and Characterization?

Andrew B. Rosenkrantz1, Xiangtian Kong2, Ben Niver1, Samir S. Taneja3, Jonathan Melamed2

1Radiology, NYU Langone Medical Center, New York, NY, United States; 2Pathology, NYU Langone Medical Center, New York, NY, United States; 3Urology, NYU Langone Medical Center, New York, NY, United States

21 patients with prostate cancer underwent prostate MRI including DWI at 1.5T prior to prostatectomy.  The native diffusion-weighted images (nDWI) and ADC map were compared, using prostatectomy as reference standard.  Compared with nDWI, the ADC map demonstrated significantly more tumor foci as well as greater relative contrast between tumor and benign PZ.  Among tumors visible on the ADC map, there was a trend toward greater Gleason score and tumor size for those also visible on nDWI.   Our data supports the importance of review of the ADC map in addition to nDWI given possible greater tumor visibility on the ADC map.

14:30         4778.     Intravoxel Incoherent Motion MR Imaging on Prostate Cancer

Yuxi Pang1,2, Baris Turkbey2, Marcelino Bernardo, 23, Wei Liu, 2,4, Vijay Shah, 23, Peter Choyke2

1Philips Healthcare, Cleveland, OH, United States; 2Molecular Imaging Program, National Cancer Institute, Bethesda, MD, United States; 3SAIC-Frederick, Frederick, MD, United States; 4Philips Research North America, Briarcliff Manor, NY, United States

Intravoxel incoherent motion (IVIM) MR imaging has the potential to separate perfusion (active blood microcirculation) from pure diffusion in DWI studies. This perfusion information is intrinsically linked with angiogenesis in tumor growth, thus, it is expected that different perfusion patterns would be found in tumors in comparison to normal tissues. In this retrospective study, we have analyzed 22 DWI data from patients with prostate cancers, and found significant increases in IVIM-related perfusion in tumors. This result suggests that the DWI-derived perfusion be a possible surrogate biomarker and a potential additional MRI parameter for accurate diagnosis of prostate cancer.

15:00         4779.     T2-Weighted MR Imaging Combined with Diffusion Weighted MR Imaging for Selection of True Active Surveillance Patients Based on Stage and Gleason Score Criteria: A Retrospective Multireader Study.

Caroline Hoeks1, Pieter Vos1, Diederik Somford2, Derya Yakar1, Thomas Hambrock1, Stijn Heijmink1, Jurgen Futterer1, Henk Vergunst3, Christina Hulsbergen-van de Kaa4, Fred Witjes2, Henkjan Huisman1, Jelle Barentsz1

1Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands; 2Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands; 3Department of Urology, Canisius Wilhelmina Hospital, Nijmegen, Gelderland, Netherlands; 4Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, Gelderland, Netherlands

Problem Undersampling of prostate cancer can lead to incorrect surveillance (AS) patient selection. Aim: to determine if T2-weighted (T2w) MRI and diffusion weighted MRI (DWI) could contribute in AS patient selection by comparing radiologist reading of stage and Gleason score(GS) to prostatectomy. Methods Twelve prostatectomy patients were retrospectively selected by biopsy criteria and a performed 3T MRI preprostatectomy.  Four radiologists scored T2w-MRI and T2w-MRI in combination with DWI. Results AUC values for T2w-MRI prediction of AS patients varied from 0,812 for inexperienced reader to 0,812-1,0 for experienced readers. Conclusion T2w-MRI could be of additional value in AS patient selection.

                                   Wednesday 13:30-15:30                                                                     Computer 105           

13:30         4780.     Relative Conspicuity of Prostate Cancer: Apparent Diffusion Coefficient Versus  Dynamic Contrast Enhancement

Daniel Jason Aaron Margolis1, Timothy McClure1, Steven Raman1

1Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE) can localize prostate cancer in situ, but it is unclear if one is superior. DWI, Ktrans, Kep, Ve, and T2WI are compared with surgical pathology in 23 patients using a unitless variable, the conspicuity ratio, the difference of the values from the ROI of the lesion and the contralateral side, divided by the average of these values. Prostate cancer is more conspicuous on DWI ADC maps and on DCE than on T2WI, and more conspicuous on DCE than on ADC, but Ktrans and Kep are not significantly different in terms of conspicuity.

14:00         4781.     Intersequence Variability in Multiparametric-Derived 3D Prostate Tumor Volumetrics at 3.0T

Fiona M. Fennessy1, Sota Oguro1, Yi Tang1, Robert V. Mulkern1, Steven Haker1, Ehud J. Schmidt1, Sandeep Gupta2, Clare M. Tempany1

1Radiology, Brigham and Women's Hospital, Boston, MA, United States; 2GE Global Research, Niskayuna,, NY, United States

Newer approaches for prostate cancer treatment mandate improvements in MR imaging to allow for accurate index lesion detection and display, to guide biopsy and focal therapy. In 9 pathology-proven prostate cancer patients, we manually segmented tumor according to multiparametric MR (mpMR) sequences using 3D-slicer software, and obtained volumetrics for each. Volumes based on DCE maps were significantly greater than those based on ADC maps (p=0.011) or T2WI (p=0.001), possibly reflecting different physiological properties of tumor assessed with mpMR. Volume discrepancies can be displayed in a single framework, and should be taken into consideration for tumor mapping in focal therapy planning.

14:30         4782.     The Utility of Prostate MRI Using Diffusion and Dynamic Enhanced Imaging in the Evaluation of Patients Previously Biopsy Negative for Cancer

Andrew Dean Hardie1

1Radiology, Medical University of South Carolina, Charleston, SC, United States

Patients with an initial set of prostate biopsies which were negative for cancer were assessed by phased array MRI. All patients subsequently had repeat prostate biopsy which was used as the gold standard. The diagnostic accuracy of MRI, negative predictive value, and the difference in the number of biopsy samples performed in patients with cancer suspected by MRI and those unlikely to have cancer by MRI were assessed. MRI was 100% sensitive, 91% specific, and had a 100% negative predictive value for cancer. Less biopsy passes were performed in patients with an MRI read as likely to have cancer than those unlikely to have cancer by MRI.

15:00         4783.     Multiparametric Prostate MR Imaging and Spectroscopy in Patients with High-Risk Localized Prostate Cancer Before Radical Prostatectomy Assesses Risk of Extracapsular Extension And/or Positive Margins.

Ernesto Castillo1,2, Emilio Hernandez3, Jose Maria Rodriguez-Barbero4, Pilar Perez Sanz1, Javier Gonzalez3, Pedro Cabrera3, Javier C. Angulo, 23

1Radiology, H.U. de Getafe, Getafe, Madrid, Spain; 2Universidad Europea de Madrid; 3Urology, H.U. de Getafe; 4Pathology, H.U. de Getafe

In 30 patients with high-risk localized (T1-2) prostate cancer the risk of extracapsular extension and affected margins before radical prostatectomy were evaluated blindly before surgery. The pathologists’ evaluation of the biopsy cylinders predicted the risk erroneously in 35% of the evaluations. Using multiparametric MRI and MR spectroscopic imaging, diffusion-weighted imaging and dynamic CE-MRI with an endorectal coil the radiologist did so in 18.3%. Multiparametric MRI of the prostate preoperatively alerts upon the risk of extracapsular disease in high-risk localized prostate cancer better than accurate review of transrectal biopsy.

                                   Thursday 13:30-15:30                                                                        Computer 105           

13:30         4784.     MR-US Fusion for Targeted Prostate Biopsy

Clifford Weiss1, Michael Seitz2, Karin Herrmann3, Arno Graser3, Berthold Kiefer4, Martin Requardt4, Jens Fehre4, Ralf Nanke4, Mamadou Diallo5, Parmeshwar Khurd5, Ali Kamen5, Wolfgang Wein5

1Center Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Urology Department, Ludwig Maximilian Universität München, München, Germany; 3Radiology Department, Ludwig Maximilian Universität München, München, Germany; 4Siemens Healthcare, Erlangen, Germany; 5Imaging & Visualization Department, Siemens Corporate Research, Princeton, NJ, United States

We aim to improve prostate targeted biopsy procedures, by taking pre-acquired diagnostic MRI images, and actively fusing them to the real-time trans-rectal ultrasound. In this way the diagnostic power of prostate MRI is married to the flexible, rapid and inexpensive ultrasound guided procedure. We propose a system based on a magnetically tracked freehand ultrasound probe, combined with a novel powerful deformable registration workflow that effectively compensates prostate organ deformation between the two modalities. We present initial results in terms of registration accuracy and clinical usefulness, from a study on 19 middle aged patients with elevated PSA and suspected prostate cancer.

14:00         4785.     Fast T2 Relaxometry in Prostate Cancer Patients at 3T

Wei Liu1, Julien Senegas2, Baris Turkbey3, Dagane Daar4, Marcelino Bernardo4, Peter Choyke3

1Clinical Sites Research Program, Philips Research North America, Briarcliff Manor, NY, United States; 2Sector of Tomographic Imaging, Philips Research Europe, Hamburg, Germany; 3Molecular Imaging Program, National Cancer Institute, Bethesda, MD, United States; 4Molecular Imaging Program, National Cancer Institute, SAIC-Frederick Inc., Bethesda, MD, United States

A fast T2 mapping technique using multi-echo spin-echo sequence with four-fold undersampling has been applied to characterize prostate T2 values in 23 patients. Utilizing the temporal and spatial correlation of T2 signal decay, folding-free images were reconstructed at each echo time providing a series of diagnostic images with variable T2-weighting. Quantitative T2 maps were generated with very good reproducibility in clinical relevant scan time. T2 values of tumor tissues were significantly lower than the normal control regions. Our results demonstrate this fast T2 relaxometry can provide an effective approach for accelerated T2 quantification in prostate patients.

14:30         4786.     Quantitative and Radiologic Evaluation of the Patient-Specific MR-Based Molds

Vijay Pravin Shah1,2, Baris Turkbey2, Thomas Pohida3, Haresh Mani4, Maria Merino4, Peter A. Pinto5, Cheng Ruida3, Matthew McAuliffe3, Peter Choyke2, Marcelino Bernardo1,6

1Imaging Physics, SAIC-Frederick, Inc, Frederick, MD, United States; 2Molecular Imaging Program, National Cancer Institute,, Bethesda, MD, United States; 3Division of Computational Bioscience, CIT, National Institutes of Health, Bethesda, MD, United States; 4Laboratory of Pathology, National Cancer Institute, Bethesda, MD, United States; 5Urologic Oncology Branch, National Cancer Institute, Bethesda, MD, United States; 6Molecular Imaging Program, National Cancer Institute, Bethesda, MD, United States

Prostatectomy specimens were processed using the Patient-specific MR-based molds (PSMRM) to improve correlation clinical MR imaging with the histopathology. In this study, we compare  in vivo  and  ex vivo  MRI of the prostate to evaluate performance of the PSMRM. The volume and surface area were measured to quantitatively evaluate fit of the specimen in the mold, while an experience radiologist performed radiology evaluation. Prostate volume shrinkage ranged from 2-25%, but we could observe good correlation between the in vivo and ex vivo MRI for most cases.

15:00         4787.     MRI of Prostate Patients in the Radiotherapy Treatment Planning Position

Scott Hanvey1, John Foster2

1Radiotherapy Physics, Beatson West of Scotland Cancer Centre, Glasgow, Lanarkshire, United Kingdom; 2MRI Physics, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom

Accurate localisation of the planning target volume (PTV) is vitally important in radiotherapy. The excellent soft tissue contrast of magnetic resonance imaging (MRI) makes it an ideal imaging modality for radiotherapy of the prostate.  Registration of MRI with CT can be problematic since the MRI table is not generally flat. The following study compared the accuracy of the registration of MRI with CT in 20 prostate patients receiving an MRI in the typical curved table and on a specially designed flat table. It also measured the PTVs of patients in the normal and radiotherapy position in MRI.

Cancer Cells & Biopsies

Hall B                        Monday 14:00-16:00                                                                           Computer 106           

14:00         4788.     Activation of Choline Kinase and Phospholipase C in HDAC Inhibition

Christopher S. Ward1, Judy Hwang1, Sabrina M. Ronen1

1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States

The aim of this study is to examine the modulation of choline metabolism by SAHA through a combination of magnetic resonance spectroscopy and enzymatic studies. This study confirmed previous findings of increased choline-related metabolites following HDAC inhibition, while providing new insight into the underlying mechanism. HDAC inhibition was associated with increases in choline kinase and phosphatidylcholine-specific phospholipase C activities, suggesting phosphocholine levels are elevated as a result of upregulation in both synthesis and catabolism.

14:30         4789.     Choline Metabolism in Basal-Like and Luminal-Like Breast Cancer Xenografts Respond Differently to Doxorubicin and Bevacizumab Treatment

Siver Andreas Moestue1, Else Marie Huuse1, Evita Lindholm2, Beathe Sitter1, Gunhild Mari Mćlandsmo2, Olav Engebrĺten2, Ingrid Susann Gribbestad1

1Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Tumor Biology, Institute for Cancer Research, Oslo, Norway

Using HR MAS MRS, the changes in choline metabolite concentrations in xenograft models of luminal-like and basal-like breast cancer were studied following treatment with bevacizumab and/or doxorubicin. The choline metabolism in the two models responded differently to the treatments.

15:00         4790.     Fluorothymidine as a Therapeutic Response Marker of the Investigational Anticancer Agent RAF265: Insights from 19F-NMR and Flow Cytometry

Andy Dzik-Jurasz1, Melissa Lin2, Kathleen Dohoney3, Jason McCormick4, Mary Ising4, Darrin Stuart5, Diana Jespersen4

1Oncology Translational Medicine, Novartis Pharmaceuticals Corporation, Inc, Florham Park, NJ, United States; 2Novartis Pharmaceuticals Corporation, Inc, NJ, United States; 3Novartis Institutes for Biomedical Research, Inc, Cambridge, MA, United States; 4Oncology Translational Medicine, Novartis Pharmaceuticals Corporation, Inc, East Hanover, NJ, United States; 5Novartis Institutes for Biomedical Research, Inc, Emeryville, CA

Fluorothymidine is used as an index of cellular proliferation in studies of therapeutic response. We used 19F-NMR to follow signal changes in cell extracts of the melanoma cell line A375M incubated with 19F-fluorothymidine and the investigational anticancer agent RAF265. Flow cytometry was used to characterize differences in cell cycle profile, count and apoptosis. A 19F-resonance tentatively assigned to a phosphate metabolite of fluorothymidine demonstrated a lower intensity in the treatment group and flow cytometry reporting a drop in the proportion of metabolically active cells exposed to drug. This approach could be used to explore the cellular changes influencing fluorothymidine signal.

15:30         4791.     Dichloroacetate Treatment Resulted in a Dramatic Drop in the Conversion of Hyperpolarised 1-13C Labelled Pyruvate to Lactate in Human Colon Carcinoma Cells

Yuen-Li Chung1, Helen Troy1, Ian R. Judson2, John R. Griffiths3, Martin O. Leach1, Thomas R. Eykyn1

1CR-UK and ESPRC Cancer Imaging Centre, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2CR-UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 3Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom

Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase (PDK) inhibitor and is found to be an anti-cancer agent. The aim of this work was to study the mechanism of action of DCA and to develop a non-invasive biomarker for response following PDK inhibition. DCA treatment caused G1 arrest and a dramatic drop in the conversion of hyerpolarised 13C-labelled pyruvate to lactate. 1H-MRS of the culture media of DCA-treated cells also showed a reduction in steady state eupolarised lactate production and increased alanine uptake.  These changes have potential as non-invasive biomarkers of drug action. DCA treatment also altered phospholipid metabolism, which could provide further biomarkers of response.

                                   Tuesday 13:30-15:30                                                                          Computer 106           

13:30         4792.     Creatine and N-Acetylaspartate Concentrations Are Associated with P53 Status in Astrocytoma

Tracy Richmond McKnight1, Kenneth J. Smith1, Susan Chang2, Mitchel S. Berger2

1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, United States; 2Neurological Surgery, UCSF, San Francisco, CA

Abnormal function of p53 protein may result in compromised DNA repair and reduced apoptosis leading to increased tumor density and resistance to DNA-damaging therapies. We hypothesized that a downstream function of p53 might be an alteration in cell metabolism. We compared the HRMAS MRS profile of astrocytoma with normal (p53wt) and abnormal (p53ab) p53.  Cre and NAA were lower and cell density was higher in p53ab tumors. No correlations were observed between any of the IHC and metabolic parameters. These findings suggest that p53 may influence the energy production and cell density of astrocytoma; however, the exact mechanisms remain unclear.

14:00         4793.     MS-275 and Letrozole Treatments Inhibit Tumor Growth and Reduce Phosphomonoesters in Triple Negative MDA-MB-231 Tumors

Tariq Shah1, Nguyen Nguyen2, Sara Sukumar2, Zaver M. Bhujwalla1

1JHU ICMIC Program, Russell H Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine , Baltimore, MD, United States; 2Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center , Johns Hopkins School of Medicine, Baltimore, MD, United States

The absence of ER/PR/Her-2/neu receptors in triple negative breast cancers makes them difficult to treat.  Histone deacetylase (HDAC) inhibitors have been found to re-express the estrogen receptor (ER).  Combining an HDAC inhibitor with hormonal treatment is therefore an attractive choice for triple negative breast cancers.  Here we have investigated the effect of the HDAC inhibitor MS-275, the aromatase inhibitor letrozole that suppresses estrogen, and their combination in vivo in a triple negative human breast cancer xenograft using proton and phosphorus MR spectroscopy. We observed a significant reduction of choline metabolites following HDAC inhibition and combined HDAC and aromatase inhibition.

14:30         4794.     Bax-Deficiency Reduces Glycolysis and Alters Metabolic Profile in Human Colorectal Carcinoma Cells

Gigin Lin1, Dow-Mu Koh1, Simon P. Robinson1, Paul Clarke2, Martin O. Leach1, Yuen-Li Chung1

1Cancer Research UK and EPSRC Cancer Imaging Centre, Institute of cancer research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 2Cancer Research UK Centre for Cancer Therapeutics, Institute of cancer research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom

Bax, a Bcl-2 family protein, plays a central role in regulating apoptosis pathways thus being a major determinant of tumour cellsŐ fate in response to cancer therapy. 4% of human colorectal carcinoma Hct116 cells are Bax-deficient and are known to be resistant to chemotherapy and TRAIL-induced apoptosis. However, there is little information available on the metabolic effects of Bax-deficiency in colorectal carcinoma cells.  We designed a 1H NMR based metabolomics study of isogenic wild type (WT) and Bax-deficient (KO) colorectal carcinoma cells, to examine the metabolic effects of Bax-deficiency in cancer cells. Many metabolic adaptations, including glycolysis, glutaminolysis, serine/purine synthesis and metabolism were found in Bax KO cells when compared with WT cells. This study indicates the functional diversity of Bax-deficiency on colorectal carcinoma Hct116 cells.

15:00         4795.     Identification of Signals from Glycosylation Precursors in 1H MR Spectra of Intact Tumour Cells

Sveva Grande1, Alessandra Palma1, Anna Maria Luciani1, Laura Guidoni1, Antonella Rosi1, Vincenza Viti1

1Dipartimento di Tecnologie e Salute, Istituto Superiore di Sanitŕ and INFN, Roma, Italy

The glycosylation process, either in the secretory pathway or in the nucleocytoplasmatic compartment, is a major post translation modification of proteins. MRS is a technique able to observe cell metabolites directly in intact cells. Carbohydrate metabolism is not fully exploited with this technique in intact systems. In a previous study we identified some relevant signals of glycosylation precursors in the low field region in intact tumor cells spectra. The present study deals with identification of signals from GalNAc in a cancer cells from adenocarcinoma of the human cervix. Treatment of cells with ammonium chloride allowed confirming signal assignment.

                                   Wednesday 13:30-15:30                                                                     Computer 106           

13:30         4796.     1H HRMAS NMR Based Metabolomics of Benign and Malignant Neuro-Endocrine Tumors and Its Comparision with Oral Cancer and Benign Gall Bladder Tissues

Shatakshi Srivastava1, Raja Roy1

1CBMR, Centre of Biomedical Magnetic Resonance, Lucknow, Uttar Pradesh, India

A comprehensive metabolic profiling of malignant and non-malignant tumors of neuro-endocrine system alongwith tumors present in other parts of body has been performed using 1H HRMAS NMR spectroscopy. The contributions of small metabolites in each kind of tumor define the mechanisms, which are critical to cellular function of a particular tissue. This may provide a better understanding of biochemical alterations in each tissue and thus, may open novel avenues of therapeutic interventions for various cancers.

14:00         4797.     Metabolite-Metabolite Correlation Maps: A Novel Method to Understand Metabolic Pathways

Basetti Madhu1, Alexandra Jauhiainen2, Masako Narita3, Simon Tavaré2, Masashi Narita3, John R. Griffiths1

1Molecular Imaging, Cancer Research UK Cambridge Research Institute, Cambridge, England, United Kingdom; 2Bioinformatics, Cancer Research UK Cambridge Research Institute, Cambridge, England, United Kingdom; 3Cellular Senescence and Tumour Suppressor Lab, Cancer Research UK Cambridge Research Institute, Cambridge, England, United Kingdom

Metabolomics studies the global metabolites in a cell, tissue or organism, and plays a vital role in understanding the cellular phenotype, and novel bioinformatic methods such as metabolite-metabolite correlation analysis are being developed  to analyse the data. 1H NMR is a useful method for obtaining metabolic profiles from cell or tissue extracts. We have recently developed a novel method of metabolite-metabolite correlation maps derived from 1H NMR based metabolomics data. These correlation maps are helpful in understanding the perturbed metabolic pathways in the cells due to the gene modifications, enzymatic modulations (inhibition/over-expression), toxic and/or drug effects and nutrient supply.

14:30         4798.     NMR Molecular Profiling of High Grade Human Glioma Reveals Distinct Metabolic Subgroups

Jose Manuel Morales1, Ana Gonzalez-Segura2, Jose Gonzalez-Darder3, Concha Lopez-Gines1, Miguel Cerda-Nicolas1, Daniel Monleon4

1Universitat de Valencia, Valencia, Spain; 2CIBER-BBN, Valencia, Spain; 3Hospital Clinico Universitario de Valencia, Valencia, Spain; 4Fundacion Investigacion Hospital Clinico Valencia, Valencia, Spain

GBM and AA are neoplasic entities of the CNS, with high biological and clinical aggressiveness. Metabolic phenotyping of high grade glioma may provide new information for better management of this disease. In this communication, we show high grade glioma molecular profiles and metabolic subgroups based on HRMAS spectra of 31 high grade glioma biopsies. One of the subgroups, which includes most AA samples, reflects a less aggressive type of tumour with lower levels of phosphocholine. Metabolic discrimination between these subgroups according to the PCA, include the levels of some metabolites which can be seen by MRS ‘in vivo’.

15:00         4799.     Phosphocholine/Glycero-Phosphocholine Ratio Is a Potential Marker for Cellular Senescence

Basetti Madhu1, Masako Narita2, Masashi Narita2, John R. Griffiths1

1Molecular Imaging, Cancer Research UK Cambridge Research Institute, Cambridge, England, United Kingdom; 2Cellular Senescence and Tumour Suppressor Lab, Cancer Research UK Cambridge Research Institute, Cambridge, England, United Kingdom

Senescence, a permanent cell cycle arrest, is thought to be a fail-safe mechanism that prevents the malignant transformation of cells; as a tumour-suppressing mechanism it shares conceptual and therapeutic similarities with the apoptosis machinery.  SA-β-gal activity, elevated p53 and p16 protein levels, coupled with morphological changes are used as senescence markers, though reliable metabolic markers for senescence are still required. We present a 1H NMR based metabolomics study of senescence induced by oncogenic Ras or MEK, or by prolonged replication, compared with growing, transformed, and quiescent cells. The data shows that phosphocholine/glycerophosphocholine ratio is a potential metabolic marker for cellular senescence.

Tumor Perfusion & Permeability

Hall B                        Monday 14:00-16:00                                                                           Computer 107           

14:00         4800.     The Influence of Cardiac Frequency on the Properties of the Arterial Input Function (AIF) and Computed DCE-MRI Parameter Values

Rickmer Braren1, Yvonne Kosanke1, Jonas Svensson2, Ernst Rummeny1, Andreas Steingoetter1

1Institute of Radiology, Klinikum rechts der Isar der TU München, Munich, Germany; 2Department of Medical Radiation Physics, Malmo University Hospital, Lund University, Malmo, Sweden

DCE-CT in combination with standard MR contrast agent allows the determination of rat population AIF. This study analyzed the impact of cardiac frequency on AIF properties detected in the rat abdominal aorta and the accompanied changes in DCE-MRI parameter values. Different anesthesia induced a change of ~100 bpm in cardiac frequency which resulted in different AIF bolus shape, recirculation and washout. These in turn induced systematic errors in tumor and muscle Ktrans of 15% or 36%, respectively. In longitudinal therapy response studies, where systemic changes, due to drug treatment, are very likely to occur this phenomenon must thoroughly be considered.

14:30         4801.     Histological Validation of the Cerebral Blood Volume Quantification in a C6 Brain Tumor Model Using RSST1-MRI with an Intravascular Contrast Agent: Gd-ACX

Adriana-Teodora Perles-Barbacaru1,2, Boudewijn Van der Sanden3, Régine Farion1, Christoph Segebarth1, Hana Lahrech1

1Functional and Metabolic Neuroimaging, Grenoble Institute of Neuroscience, Grenoble, France; 2Caltech Brain Imaging Center, Beckman Institute, Pasadena, CA, United States; 3Rayonnement Synchrotron et Recherche Médicale, Grenoble Institute of Neuroscience, Grenoble, France

The cerebral blood volume fraction (CBVf) quantification by MRI remains complex in the tumor due to the contrast agent (CA) leakage through the blood brain barrier. Gd-ACX (α-cyclodextrin complexed to gadolinium), a novel CA was shown to remain in the vascular space in a C6 brain tumor model and was used for CBVf mapping in microvasculature permeable for Gd-DOTA. Here, the use of Gd-ACX for tumor CBVf quantification was validated using histological vascular morphometry. After selecting the tumor vessels perfused by the Hoechst dye, we found a quantitative equivalence for the CBVf obtained by MRI and by vascular morphometry.

15:00         4802.     Effects of Reference Tissue AIF Derived from Low Temporal Resolution DCE-MRI Data on Pharmacokinetic Parameter Estimation

Marieke Heisen1, Xiaobing Fan2, Johannes Buurman3, Bart M. ter Haar Romeny1

1Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands; 2Radiology, The University of Chicago, Chicago, IL, United States; 3Healthcare Informatics, Philips Healthcare, Best, Netherlands

Quantitative pharmacokinetic analysis of dynamic contrast enhanced (DCE) MRI clinical data is important for detection and diagnosis of cancer.  For breast imaging, however, data is often acquired at low temporal resolution to enable high-spatial resolution coverage of both breasts.  The effect of arterial input functions derived from low temporal resolution data on estimation of Ktrans and ve was investigated by downsampling high temporal resolution pre-clinical data in k-space.  The results demonstrate that using a reference tissue AIF extracted from low temporal resolution data (till T ˇÖ 60 s) is feasible and could be used to quantitatively analyze DCE-MRI data.

15:30         4803.     Dynamic Contrast-Enhanced (DCE)-MRI with Gadobutrol for Monitoring Sorafenib Effect on Experimental Prostate Carcinomas

Clemens Christian Cyran1, Philipp Marius Paprottka1, Bettina Schwarz2, Jobst von Einem1, Steven Sourbron1, Olaf Dietrich1, Rabea Hinkel3, Christiane J. Bruns2, Hubertus Pietsch4, Bernd J. Wintersperger1, Maximilian F. Reiser1, Konstantin Nikolaou1

1Institute of Clinical Radiology, Munich University Hospitals - Campus Grosshadern, Munich, Germany; 2Department of Surgery, Munich University Hospitals - Campus Grosshadern, Munich, Germany; 3Department of Cardiology, Munich University Hospitals - Campus Grosshadern, Munich, Germany; 4Contrast Media Research, Bayer Schering Pharma AG, Berlin, Germany

The purpose of this study was to investigate the effects of Sorafenib on experimental prostate carcinomas in rats by dynamic MRI enhanced with Gadobutrol. Target parameters were tumor perfusion and tumor endothelial permeability. Tumor perfusion (ml/100ml/min), assayed by DCE-MRI enhanced with the small molecular contrast medium Gadobutrol, decreased significantly (p<0.01) in experimental prostate carcinomas treated with a daily, one-week treatment course of Sorafenib (10mg/kg bodyweight). In the control group, tumor perfusion increased significantly (p<0.05) over the experimental course of 7 days. No significant change was observed regarding the endothelial permeability in tumors, neither in the therapy nor in control group.

                                   Tuesday 13:30-15:30                                                                          Computer 107           

13:30         4804.     Assessment of Tumor Microvasculature by a Kinetic Model Independent DCE-MRI Method Using a High Molecular Weight Contrast Agent

Wenlian Zhu1, Yoshinori Kato1, Shruthi Shankar1, Zaver Bhujwalla1, Dmitri Artemov1

1ICMIC Program, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, United States

The goal of this study is to identify a DCE-MRI method that can minimize the effect of water exchange and blood flow on the assessment of tumor microvasculature.  This was achieved with a 3D FLASH method using a short recovery delay, a high flip angle, and non selective saturation pulses followed by crusher gradients.  Such method can help to establish a reliable method to monitor tumor vascular response to therapy.  Preliminary results are reported for a preclinical breast cancer model treated with bevacizumab.

14:00         4805.     Is It "Safe" to Use a Population Arterial Input Function for DCE-MRI in Mice?

Mary E. Loveless1,2, Jane Halliday3, Carsten Liess4, Lei Xu5, Richard Dortch, 2,6, Jennifer Whisenant, 2,7, John C. Waterton4, John C. Gore, 2,6, Thomas E. Yankeelov, 2,6

1Biomedical Engineering, Vanderbilt University, Nashville, TN, United States; 2Institute  of Imaging Science, Vanderbilt University, Nashville, TN, United States; 3Imaging, Translational Sciences, AstraZeneca, Macclesfield , Cheshire, United Kingdom; 4Imaging, Translational Sciences, AstraZeneca, Macclesfield, Cheshire, United Kingdom; 5Biostatistics, Vanderbilt University, Nashville, TN, United States; 6Radiology and Radiological Science, Vanderbilt University, Nashville, TN, United States; 7Chemical & Physical Biology, Vanderbilt University, Nashville, TN, United States

In the quantitative analysis of DCE-MRI data, the contrast agent concentration time course in the blood plasma (AIF) is required. In this study we compare parameters resulting from two common DCE-MRI models driven by both individual and population derived AIFs in mice for two different contrast agents, Gd-DTPA and P846.  The goal is to determine how the individual and population AIF derived parameters compare and how this affects the number of animals that would be needed in a given study.

14:30         4806.     Structural Spectroscopic Analysis of Tumor Vasculature Before and After Contrast Agent Administration to Mice

Gilberto S. Almeida1,2, Ian Wilson1,2, Lance Farr3, Ross J. Maxwell1,2

1Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom; 2Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom; 3Osteotronix Ltd, Swansea, United Kingdom

The aim of this study was to estimate the dimensions of vascular features in animal tumour models (HT29 colon carcinomas in mice) using a combination of structural spectroscopy analysis and contrast agent uptake. Structural spectroscopy data were acquired from rectangular prisms across the tumour using a one-dimensional spin-echo pulse sequence at 7T. The signal profiles were analyzed to determine the size distribution of the anatomical elements of interest before and 10 min after injection of gadoteridol. There was a clear difference in the intensity of structural features (dimensions 10-20 mm-1) after injection of contrast agent.

15:00         4807.     Radial Multi Gradient Echo DCE-MRI for 3D Ktrans Mapping with Individual AIF Measurement in Mouse Tumor Models

Julien Vautier1,2, Christine Walczak1,2, Nadine El Tannir El Tayara1,2, Andreas Volk1,2

1U759 INSERM, Orsay, France; 2Institut Curie, Orsay, France

This study presents proof of concept for a new 3D radial DCE-MRI technique well adapted to preclinical studies of microvasculature in mouse tumor models experiencing respiratory motion. The technique measures R2*-corrected R1 (t). It is based on an interleaved 2D and 3D radial multi gradient echo acquisition to provide simultaneously the AIF on the heart at high temporal resolution (2s) and 3D data on the tumor at a lower time resolution (2min). 3D Ktrans maps were obtained in colorectal tumor xenografts subcutaneously implanted at the abdominal level.

                                   Wednesday 13:30-15:30                                                                     Computer 107           

13:30         4808.     Prediction of Disease Specific Survival in Patients with Head and Neck Cancer Using Dynamic MRI

Sanjeev Chawla1, Sungheon Kim2, Laurie A. Loevner1, Harry Quon3, Wei T. Hwang4, G Weinstein5, A Chalian1, Harish Poptani1

1Radiology, University of Pennsylvania, Philadelphia, PA, United States; 2Radiology, New York University, New York, NY, United States; 3Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States; 4Biostatistics, University of Pennsylvania, Philadelphia, PA, United States; 5Otorhinolaryngology, University of Pennsylvania, Philadelphia, PA, United States

We evaluated the potential of pretreatment volume transfer constant (Ktrans) from DCE-MRI in predicting disease specific survival in patients with squamous cell carcinomas of head and neck. Sixty-six patients underwent chemo-radiation therapy and were followed up clinically (median follow up time for the surviving patients was 24.0 months).  Pretreatment median Ktrans was used as threshold value to separate patients into two groups (above and below the threshold value). The survival for patients with higher pre-treatment Ktrans was significantly prolonged compared to patients with lower Ktrans value indicating that Ktrans can be used to predict survival outcome in these patients.

14:00         4809.     Quantitative Correlation of Volume Transfer Coefficient Ktrans with Histopathologic Grades of Gliomas

Na Zhang1,2, Zhengsheng Deng2, Li Meng3, XiaoYi Wang3, Weihua Liao3, Bob L. Hou4

1Paul C. Lauterbur Research Center for Biomedical Imaging,Paul C. Lauterbu, Chinese Academy of Science , Shenzhen, Guangdong, China; 21Institute of Biomedical Engineering, School of Info-physics and Geomatics Engineering,, Central South University, Changsha, Hunan, China; 3Department of Radiology, XiangYa Hospital of School of Medicine, Central South University, Changsha, Hunan, China; 4Radiology, West Virginia University, Morgantown, WV, United States

The breakdown of blood-brain barrier (BBB) in gliomas results in the increment of microvascular permeability: a surrogate marker to assess malignant degree of gliomas. The volume transfer coefficient of contrast agent (CA) from plasma space to extravascular extracellular space (EES), as defined Ktrans, has been used to characterize the microvascular permeability quantitively. Since knowing the grades of gliomas for administration of the tumor treatments is very important, and there were only few reports for applying T1 perfusion MRI data for evaluating grades of glioma, in current study we presented the results of correlation of Ktrans and histopathologic grades of gliomas by using the T1-weighted dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) method and a modified Tofts' model, and also investigated to apply Ktrans, Kep, Kel, Ve, and Vp obtained from the T1 perfusion data analyses for evaluating grades of the gliomas.

14:30         4810.     Diffusion-Weighted MRI and Dynamic Contrast-Enhanced MRI of Bladder Cancer at 3T

Huyen Thanh Nguyen1,2, Guang Jia1, Zarine Shah1, Mitva Patel1, Peter Wassenaar1, Steffen Sammet1, Amir Mortazavi3, Karmal Pohar4, Cathy Mojzisik1, Michael Knopp1

1Department of Radiology, The Ohio State University, Columbus, OH, United States; 2Biophysics Program, The Ohio State University, Columbus, OH, United States; 3Department of Internal Medicine, The Ohio State University, Columbus, OH, United States; 4Department of Urology, The Ohio State University, Columbus, OH, United States

This on-going study evaluates the ability of Diffusion-Weighted MRI (DWI) and Dynamic Contrast-Enhanced MRI (DCE-MRI) to diagnose bladder tumors and the consistency between the two sequences. Preliminary results from this study show that DWI and DCE-MRI are effective to detect bladder cancer. With these promising preliminary results, the combination can be continued to study the alteration of tumor characteristics after neoadjuvant therapy and the most importantly to help stage bladder tumors. In addition, DWI performed with high b-factors can be supportive to the differentiation of bladder tumors from surrounding tissues.

15:00         4811.     Quantitative Osteosarcoma DCE-MRI: How Long Is the Acquisition Time Necessary?

Ya Wang1, Wei Huang2, David M. Panicek1, Laurence H. Schwartz1, Jason A. Koutcher1

1Memorial Sloan Kettering Cancer Center, New York, NY, United States; 2Oregon Health & Science University, Portland, OR, United States

Based on actual Ktrans and Ve values from 18 osteosarcoma patients, simulated DCE-MRI time-courses were reconstructed with varying scan time length to estimate minimal acquisition time needed to derive accurate and stable pharmacokinetic parameters.  The results suggest that for typical osteosarcoma necrosis percentage range, 5 min DCE-MRI scan time is adequate.

                                   Thursday 13:30-15:30                                                                        Computer 107           

13:30         4812.     Defining Adequate Complexity of Compartment Models in DCE-MRI

Julia Catarina Kärcher1, Volker Johann Schmid1

1Department of Statistics, Ludwig-Maximilians-University, Munich, Germany

Standard one compartment models used for the quantitative analysis of concentration time series in DCE-MRI fail in modeling heterogeneity. We propose a model with two tissue compartments that accounts for heterogeneity within voxels and thus more appropriately describes the uptake behavior at tumor margins. We propose a model selection criterion that accounts for the adequacy both of model fit and of model complexity. DCE-MRI scans from breast cancer data are evaluated with the proposed model selection criterion per voxel: at tumor margins the proposed two tissue compartment model outperforms the standard one compartment model.

14:00         4813.     Cross-Visit Tumour Sub-Segmentation May Reveal Localised Response to Anti-Angiogenic Treatment in DCE-MRI Data

Giovanni Alessandro Buonaccorsi1, Caleb Roberts1, James O’ Connor1, Chris Rose1, Sue Cheung1, Yvonne Watson1, Karen Davies1, Lynn Hope2, Alan Jackson1, Gordon Jayson2, Geoff Parker3

1Imaging Science and Biomedical Engineering, University of Manchester, Manchester , United Kingdom; 2Cancer Research UK Dept of Medical Oncology, Christie Hospital, Manchester, United Kingdom; 3Imaging Science and Biomedical Engineering, University of Manchester, Manchester, United Kingdom

Using DCE-MRI data from four patients enrolled in a trial of a VEGF inhibitor, we performed cross-visit tumour sub-segmentations to obtain cluster volumes and localised cluster VOI statistics for Ktrans.  In each tumour a subset of clusters showed statistically significant post-treatment volume changes for at least one visit.  Eight of 9 clusters with decreased volume had mean Ktrans > 0.127 min-1.  Reduced post-treatment volume in clusters with “high” Ktrans is consistent with reduced volume of actively-angiogenic tumour regions, as would be expected with a VEGF inhibitor.  These effects would not be evident when using whole tumour VOI statistics.

14:30         4814.     Dynamic Contrast-Enhanced T1 -Weighted Perfusion MRI Differentiates Tumor Recurrence from Radiation Necrosis: Relative Cerebral Blood Volume Measurements and FDG-PET Validation

Vibeke Andrée Larsen1, Helle Juhl Simonsen2, Ian Law3, Henrik Pedersen2, Henrik BW Larsson2, Adam Espe Hansen2

1Dept. of Radiology, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark; 2Functional Imaging Unit, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark; 3PET and Cyclotron Unit, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

The use of perfusion MRI for tumor characterization is complicated by the blood brain barrier deficiency. This preliminary study provides evidence that dynamic contrast enhanced T1 weighted perfusion imaging can distinguish radiation-induced necrosis from tumor recurrence. We studied 9 patients after radiation treatment for gliomas and the results were validated with the FDG-PET gold standard. For 10 contrast enhancing lesions, 2 metabolically inactive lesions had relative cerebral blood volume (rCBV) of less than 1.7, whereas 8 active lesions had rCBV greater than 2.0.

15:00         4815.     Relationship Between VEGF Receptor Expression and DCE-MRI Tracer Kinetic Parameters in Advanced Ovarian Cancer

Caleb Roberts1,2, Claire L. Mitchell3, James P. O'Connor, 23, Yvonne Watson1,2, Sue Cheung1,2, Alison Backen4, Caroline Dive4, Alan Jackson1,2, Gordon C. Jayson3, Geoff J. Parker1,2

1Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, The University of Manchester, Manchester, United Kingdom; 2The University of Manchester Biomedical Imaging Institute, The University of Manchester, Manchester, United Kingdom; 3Cancer Research UK Dept Medical Oncology, Christie Hospital and University of Manchester, Manchester, United Kingdom; 4Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester, United Kingdom

The integration of imaging strategies such as dynamic contrast-enhanced MRI (DCE-MRI) in early phase drug development can help elucidate the underlying tumor physiology and assess drug efficacy. This study focuses on the relationships between serological expression of soluble VEGF receptors and DCE-MRI tracer kinetic parameters in a group of ovarian tumors.  We observe striking relationships between the serological markers, Ktrans and vp that indicate that DCE-MRI is sensitive to specific aspects of the angiogenic process in these tumors.

Cancer Preclinical Studies of Animal Models

Hall B                        Monday 14:00-16:00                                                                           Computer 108           

14:00         4816.     Dynamic Oxygen-Enhanced T1-Weighted MR in Mouse Tumour Xenografts. Comparison Between Oxygen-Enhanced MRI and DCE-MRI.

Inna V. Linnik1,2, Neil Woodhouse3, Marietta Scott3, Carsten Liess3, Jean J. Tessier3, Hervé Barjat3, Geoffrey J.M. Parker1,4, John C. Waterton3,5, Josephine H. Naish1,4

1Imaging Science and Biomedical Engineering, School of Cancer and Imaging Sciences, University of Manchester, Manchester, United Kingdom; 2Biomedical Imaging Institute, University of Manchester,  Manchester, United Kingdom; 3Imaging, Translational Sciences, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom; 4Biomedical Imaging Institute, University of Manchester, Manchester, United Kingdom; 5 Biomedical Imaging Institute, University of Manchester, Manchester, United Kingdom

Recent studies have suggested that oxygen-enhanced (OE) MRI can potentially be used for assessing regional changes of oxygen delivery and accumulation in tumours when switching from breathing air to 100% oxygen, based on T1-shortening due to dissolved molecular oxygen. However while many tumours do show the domains with expected R1 increase, we have previously observed regions exhibiting apparent R1 reduction.

The aim of this study was to characterise the R1-increasing and R1-decreasing parcellations in OE-MRI in terms of their DCE-MRI response.  DCE-MRI data exhibit high Gd-DTPA uptake in the R1-increasing domains and low contrast uptake - in the R1-decreasing domains.

14:30         4817.     Investigating the Effect of Size and Site of Implantation on Tumour Vascular Morphology and Function Using Combined Carbogen USPIO (CUSPIO) Imaging

Jake Samuel Burrell1, Jane Halliday2, Simon Walker-Samuel3, John C. Waterton2, Jessica Boult1, Yann Jamin1, Lauren C. Baker1, Simon P. Robinson1

1The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2AstraZeneca, Manchester, United Kingdom; 3UCL, London, United Kingdom

Tumour vascular morphology and function is dependent on both tumour size and site of implantation. Perturbation of tissue R2* by carbogen gas (95% O2, 5% CO2) breathing, or ultra small paramagnetic iron oxide (USPIO) particle injection offers biomarkers for tumour oxygenation, and blood volume respectively. Using a combined carbogen USPIO imaging protocol, tumour δR2* during carbogen breathing, and after injection of USPIO particles was found to be significantly different in small and large subcutaneous, and orthotopic PC3 prostate tumours. This has implications when considering both drug delivery, and extent of tumour oxygenation during drug trials

15:00         4818.     Non-Invasive Assessment of Vascular Changes in an Animal Model of Breast Cancer Bone Metastases After Treatment with an Integrin Antagonist Using DCE-MRI

Dorde Komljenovic1, Maximilian Merz1, Wolfhard Semmler1, Tobias Bäuerle1

1Medical Physics in Radiology, DKFZ, Heidelberg, Germany

Breast cancer frequently metastasizes to the skeleton, resulting in predominantly osteolytic lesions causing pain and fracture. In bone metastases, αvβ3 integrin is significantly up-regulated on activated endothelial cells and recognized as an important factor in bone resorption. Furthermore, αvβ5 integrin is expressed on various breast cancer cells, including the human breast cancer cell line MDA-MB-231. In this study, we have investigated effects of the inhibition of αvβ3 and αvβ5 integrins in bone metastases by employing a small molecule antagonist of this integrin subclass. Further, our aim was to elucidate whether therapeutic effects, visualized and quantified using dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and flat panel volumetric computed tomography (VCT), allow early prediction of treatment response in experimental breast cancer bone metastases.

15:30         4819.     Monitoring Treatment Response to an Anti-Angiogenic Therapy in Experimental Breast Cancer Bone Metastases Using DWI, DCE-MRI and VSI

Maximilian Merz1, Dorde Komljenovic1, Wolfhard Semmler1, Tobias Bäuerle1

1Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany, Germany

Imaging treatment response of bone metastases is pivotal for clinical practice. The most recent version of the response evaluation criteria in solid tumors (RECIST) recommends measuring the osteolytic bone lesion by CT and the respective soft tissue tumor by MRI. However, changes in morphology and lesion size are usually observed months after the initiation of treatment. In our study we report that non-invasive imaging of tumor cellularity by DWI as well as tumor vasculature by DCE-MRI and VSI serves as an early quantifiable biomarker for the assessment of treatment response to an anti-angiogenic therapy in experimental breast cancer bone metastases.

                                   Tuesday 13:30-15:30                                                                         Computer 108           

13:30         4820.     Multimodality Characterization of a Bone-Metastasis Model

Dmitri Artemov1, Kristy L. Weber2, Yoshinori Kato1, Wenlian Zhu1, Zaver M. Bhujwalla1

1JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Department of Orthopedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Metastasis is the leading cause of mortality from cancer.  For several cancers, the bone is a major site of bulk disease from metastasis.  While multimodality imaging of subcutaneous preclinical tumor models are becoming fairly routine, the application of multi-modality imaging to bone-metastasis models is a challenge.  However, multi-modality imaging of such models can provide a wealth of information on the microenvironment, vasculature, and metabolism of bone metastasis that can used to improve treatment outcome and identify new strategies for treatment.  Here we present multi-modal imaging characterization of a well-established bone metastasis model.

14:00         4821.     Towards a Better Understanding of Bone Metastatic Pain: A Multimodal Micro-Imaging Approach

Louis Dore-Savard1,2, Luc Tremblay3,4, Melanie Archambault3,4, Jean-François Beaudoin3,4, Nicolas Beaudet1,2, Eric E. Turcotte3,4, Roger Lecomte3,4, Philippe Sarret1,2, Martin Lepage3,4

1Physiologie et biophysique, Universite de Sherbrooke, Sherbrooke, Quebec, Canada; 2Centre des Neurosciences de Sherbrooke, Sherbrooke, Quebec, Canada; 3Médecine nucléaire et radiobiologie, Universite de Sherbrooke, Sherbrooke, Quebec, Canada; 4Centre d'imagerie moléculaire de Sherbrooke, Sherbrooke, Quebec, Canada

A better understanding of the mechanisms underlying the genesis of bone cancer pain is clearly needed. We used a multimodal imaging protocol combining μCT and MRI-PET co-registration in a novel murine bone cancer pain model. Interestingly, we consistently detected bone tumor before pain behavior were observable. Moreover, MRI, Na18F and 11C-methionine PET provided us with complementary information allowing the visualization of compensative bone formation, inflammation, tumor metabolism and extensive damage in bone microenvironment. This model and our imaging approach will help the understanding of metastatic bone pain and facilitate the development of improved analgesic therapy.

14:30         4822.     Using MRI to Monitor Tumorigenesis in a Murine Model of Melanoma Brain Metastasis

Amr Morsi1,2, Evelyn Voura1,2, Susan Pun2, Minh Dung Hoang2, Asad Baig3, Erik Parker1, John Golfinos1, Youssef Zaim Wadghiri2

1Neurosurgery, NYU langone medical center, NYC, NY, United States; 2RADIOLOGY, NYU langone medical center, NYC, NY, United States; 3Radiology, NYU langone medical center, NYC, NY, United States

Our group at NYU medical center tried to establish a murine model of melanoma brain metastasis and implement an MRI protocol to longitudinally follow the metastatic tumor over time which will aid in therapeutic studies. Although the established model spread to unconventional sites ( intra-ventricular and meningeal) instead of parenchymal, the MRI studies conducted showed promising results since it echoed the MRI characteristic findings observe in clinical settings.

15:00         4823.     Monitoring Metastases in a Mouse Model of Ewings Sarcoma Using DWIBS

Cornelius Faber1, Marc Hotfilder2, Sareeta Kailayangiri2, Hendrik Kooijman3, Uta Dirksen2, Claudia Rössig2, Volker Vieth1

1Department of Clinical Radiology, University Hospital Muenster, Muenster, Germany; 2Department od Pediatric Hematology and Oncology, University Hospital Muenster; 3Philips Health Care

Diffusion-weighted Whole-body Imaging with Body background signal Suppression (DWIBS) was implemented in a mouse model of Ewings Sarcoma on a clinical 3 T scanner. Metastasis formation could be detected and monitored over a period of four weeks. 3D MIP reconstruction of DWIBS data allowed for fast identification of metastases and provided additional information (ADC) as compared to STIR, T1 and T2 weighted images, supporting a more reliable lesion classification. DWIBS may serve as a valuable asset to the tools for characterizing cancer models in mice.

                                   Wednesday 13:30-15:30                                                                     Computer 108           

13:30         4824.     A Comparative Study of Frequency and Time Domain Data Analysis of HR-MAS 1H NMR Data from ApcMin/+ Mouse Gut Tumours

Basetti Madhu1, Santiago Uribe Lewis2, Adele Murrell2, John R. Griffiths1

1Molecular Imaging, Cancer Research UK Cambridge Research Institute, Cambridge, England, United Kingdom; 2Epigenetics Imprinting, Cancer Research UK Cambridge Research Institute, Cambridge, England, United Kingdom

In this study we compared HR-MAS 1H NMR spectroscopy data of mouse gut tumour tissue biopsies obtained by time domain (ER-QUEST) and frequency domain (LCModel) analysis methods., Our results show that LCModel fitting resulted in either equal or smaller fractional uncertainties in the estimates of metabolites in comparison to the ER-QUEST method. The LCModel method also showed greater ease and robustness in the fitting of HR-MAS 1H NMR data from the experimental tumours.

14:00         4825.     Correlation Between TCho Peak at H-MRS and Gene Expression of Choline Kinases and Transmembrane Choline Transporters: An Experimental Study on a Rodent Rhabdomyosarcoma Model Using a Standard 3T Clinical Imager

Denis Rommel1, Frank Peeters2, Jorge Abarca-Quinones2, Christine De Saeger3, Isabelle Leclercq3, Thierry Duprez1

1Radiology, Université Catholique de Louvain, Brussels, Belgium; 2Radiology, Université Catholique de Louvain, Belgium; 3Gastro-enterology, Université Catholique de Louvain, Brussels, Belgium

We investigated which from transmembrane choline transporters and choline kinases had the most prominent role in the elevation of the tCho peak at H-MRS using a rodent rabdomyosarcoma model. tCho peak was quantified as the area under the curve at 3.2 ppm obtained on a 3T clinical system, and gene expression was quantified by PCR after reverse transcription into cDNA using standard ΔCt calculations with reference to RPL19 gene expression.  The prominence of the choline kinase α expression versus that of the transmembrane choline transporters was strongly suggested by the statistical analysis.

14:30         4826.     Characterization of Two High Grade Human Oligodendroglioma Mouse Models Using  1H MRSI

Bob C. Hamans1, An Claes2, William P. Leenders2, Arend Heerschap1

1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Here we characterize two human oligodendroglioma xenograft models by their metabolic profile using 1H MRSI and compare the findings to previously published human oligodendroglioma data. Particular metabolic differences were observed between the xenograft oligodendroglioma lines indicating the possibility to differentiate high to low grade glioma in these models using 1H MRSI.

15:00         4827.     1H MRS Metabolite Profiles of Medulloblastomas in Transgenic SMO Mice

Khan S. Hekmatyar1, Martin Wilson2, Neil Jerome3, Julian L. Griffin4, Andrew Peet2, Risto A. Kauppinen1

1Radiology, Dartmouth Medical School, Hanover, NH, United States; 2University of Birmingham, United Kingdom; 3Dartmouth Medical School, United States; 4Biochemistry, University of Cambridge, United Kingdom

Aberrant hedgehog signaling is implicated in generation of human medulloblastomas. We have used smoothened receptor (SMO) transgenic mice with high incidence of spontaneous medulloblastomas to characterize 1H MRS metabolic profiles in tumours with known molecular pathology. Medulloblastomas in the SMO mice showed very low NAA, low GABA and myo-inositol and high taurine, total cholines, scyllo-inositol and glycine. It appears that taurine, cholines and scyllo-inositol are potential common MRS biomarkers for medulloblastomas, whereas myo-inositol, GABA and glycine may be more associated with aberrant SMO signaling in medulloblastomas.

                                   Thursday 13:30-15:30                                                                        Computer 108           

13:30         4828.     Investigating δR1 and δR2* as Biomarkers of Tumour Oxygenation

Jake Samuel Burrell1, Jane Halliday2, Simon Walker-Samuel3, John C. Waterton2, Jessica Boult1, Yann Jamin1, Lauren C. Baker1, Simon P. Robinson1

1The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2AstraZeneca, Manchester, United Kingdom; 3UCL, London, United Kingdom

Carbogen-induced changes in R1, sensitive to dissolved paramagnetic molecular oxygen in the blood, and R2*, dependent on paramagnetic deoxyhaemoglobin, were determined in the same murine GH3 prolactinomas.  Carbogen significantly increased R1 and reduced R2* in all tumours.  A weak yet statistically significant positive correlation was determined between δR1 and δR2*.  Tumour regions exhibiting a large reduction in R2* yet small δR1 may indicate hypoxic tumour tissue.  The combined use of δR1 and δR2* may prove more informative for the assessment of tumour hypoxia.

14:00         4829.     Evaluation and Immunohistochemical Qualification of Carbogen-Induced δR2* as a Non-Invasive Imaging Biomarker of Improved Tumour Oxygenation

Lauren CJ Baker1, Jessica K.R. Boult1, Yann Jamin1, Lesley D. McPhail1, Simon Walker-Samuel1, Jake S. Burrell1, Margaret Ashcroft2, Franklyn A. Howe3, John R. Griffiths4, James A. Raleigh5, Albert J. van der Kogel6, Simon P. Robinson1

1The Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2University College London, London, United Kingdom; 3St. George's, University of London, London, United Kingdom; 4Cambridge Cancer Institute, Cambridge, United Kingdom; 5University of North Carolina, Chapel Hill, United States; 6University of Nijmegen Medical Centre, Nijmegen, Netherlands

The transverse relaxation rate R2* (s-1) of GH3 prolactinomas was quantified whilst the host breathed air and subsequently carbogen (95%O2/5%CO2), and the data compared with quantitative immunohistochemical analysis of uptake of two hypoxia markers, CCI-103F, administered whilst the host breathed air, and pimonidazole, administered during subseqent carbogen breathing, within the same tumour.  A significant reduction in R2* with carbogen breathing was associated with a significant reduction in pimonidazole staining, providing further validation of carbogen-induced δR2* as a non-invasive imaging biomarker of increased tumour oxygenation.

14:30         4830.     Gas-Challenge Blood Oxygen Level Dependent (BOLD) MRI for Quantitative Assessment of Tumor Necrosis in Rodent Hepatoma Model

Yang Guo1, Ning Jin1,2, Rachel Klein1, Guang-Yu Yang3, Reed Omary1,2, Andrew Larson1,2

1Department of Radiology, Northwestern University, Chicago, IL, United States; 2Department of Biomedical Engineering , Northwestern University, Chicago, IL, United States; 3Department of Pathology, Northwestern University, Chicago, IL, United States

Assessment of tumor necrosis is important for evaluating tumor treatment response. Gas-challenge (GC) blood oxygen level dependent (BOLD) MRI may permit tissue characterization without the need for exogenous contrast agents. For our study, we tested the feasibility of using GC-BOLD MRI to assess tumor necrosis fraction and compare to reference standard histological measurements in a rodent N1-S1 hepatoma model and found a significant positive correlation between gold-standard histology and GC-BOLD measured necrotic fraction. GC-BOLD MRI might serve as a non-invasive surrogate for early assessment of therapy response (prior to conventional anatomic size changes).

15:00         4831.     In Vivo Measurement of Tumor Oxygen Consumption by 19F-MRI Relaxometry

Caroline Diepart1, Julie Magat1, Bénédicte Jordan1, Bernard Gallez1

1UCL, Brussels, Belgium

In this study, we developed a method based on 19F-MRI relaxometry for mapping the oxygen consumption in tumors. The protocol was based on the measurement of pO2 during a carbogen challenge protocol. The hyperthyroid mice provided ideal models with tissues presenting differences in oxygen consumption rates. The histogram of the 19F MRI data showed a shift to the higher oxygen consumption rates for the hyperthyroid tumors. For each tumor, we obtained a color map created from the 19F MRI data, reflecting the heterogeneity in oxygen consumption. 19F-MRI relaxometry allows the non invasive mapping of the oxygen consumption in tumors.

Tumor Therapy Response:  Preclinical & Clinical

Hall B                        Monday 14:00-16:00                                                                           Computer 109           

14:00         4832.     Two Vascular Disrupting Agents at a Clinically Equivalent Dose on Rodent Liver Tumors: Comparison of Therapeutic Outcomes with Multiple MRI Biomarkers

Huaijun Wang1, Junjie Li1, Feng Chen1, Frederik De Keyzer1, Jie Yu1, Yuanbo Feng1, Yansheng Jiang1, Guy Marchal1, Yicheng Ni1

1Department of Radiology, Catholic University of Leuven, Leuven, Vlaams Brabant, Belgium

This study aimed to compare tumoricidal events after 2 lead vascular- targeting-agents (VDAs), Combretastatin-A-4-phosphate (CA4P) and ZD6126 at a clinically-equivalent-dose (CED) in tumors with multiple MRI biomarkers correlated with postmortem microangiography and histopathology. Rhabdomyosarcomas in rat liver were treated with either VDA. Therapeutic outcomes were evaluated morphologically and functionally with 1.5T-MRI. Diffusion-weighted-imaging and dynamic-contrast-enhanced-MRI successfully monitored vascular-shutdown at 1h after VDA treatment, prior to the advent of morphological change of tumor size at 120h, which was verified with postmortem techniques. CED of CA4P has longer vascular-shutdown effect until 48h than ZD6126, leading to significantly different tumor growth delay at 120h.

14:30         4833.     Evaluation of the Effect of Anti-Angiogenic Therapy on Tumor Vasculature in Breast Cancer Mouse Xenograft

Yoshinori Kato1, Wenlian Zhu1, Shruthi Shankar1, Venu Raman1, Susanta K. Sarkar2, Zaver M. Bhujwalla1, Dmitri Artemov1

1JHU ICMIC Program, The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; 2Medicines Development, Oncology R&D, GlaxoSmithKline, Collegeville, PA, United States

The biological mechanisms underlying anti-angiogenic therapy when used in combination with conventional cytotoxic treatment are still not entirely understood.  We have evaluated the effect of anti-angiogenic therapy on tumor vasculature with MRI and tumor hypoxia with optical imaging.  Anti-angiogenic therapy transiently decreased tumor hypoxia, but induced tumor hypoxia post-treatment possibly due to the reduction of vascular volume in the tumor.  Our results provide further insights as to whether anti-angiogenic therapy induces the normalization of the tumor vasculature, which improves drug delivery by reducing hypoxia, an important environmental factor in tumor resistance.

15:00         4834.     Response of a Human Melanoma Xenograft Model to the MEK Inhibitor AZD6244 (ARRY-142886) Evaluated by Diffusion-Weighted MRI

Mounia Beloueche-Babari1, Yann Jamin1, Vaitha Arunan1, Simon Walker-Samuel1, Paul D. Smith2, John C. Waterton2, Jane Halliday2, Martin O. Leach1, Simon P. Robinson1

1Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2AstraZeneca, Macclesfield, Cheshire

Down-modulation of the BRAF-MEK-ERK1/2 signalling pathway is a novel strategy for targeted cancer treatment that causes tumour growth inhibition and induction of apoptosis. Diffusion-weighted MRI was used to detect pharmacodynamic biomarkers of treatment with the MEK inhibitor AZD6244. Treatment of a human melanoma xenograft model with AZD6244 caused inhibition of tumour growth that was associated with an increase in the apparent diffusion coefficient and tumour necrosis.

15:30         4835.     Early Detection of Treatment Response to Antiangiogenic Therapy Using IVIM-DWI in Mouse Model of Breast Cancer

Sungheon Kim1, Lindsey DeCarlo2, Gene Y. Cho1, Jens H. Jensen1, Daniel K. Sodickson1, Silvia Formenti3, Robert J. Schneider2, Eric E. Sigmund1

1Center for Biomedical Imaging, Radiology, New York University, New York, NY, United States; 2Microbiology, New York University, New York, NY, United States; 3Radiation Oncology, New York University, New York, NY, United States

This study was to investigate the feasibility of using Intra-Voxel-Incoherent-Motion (IVIM) diffusion weighted imaging (DWI) to detect the early onset of tumor vascular normalization induced by an antiangiogenic therapy. BALB/c mice with 4T1 tumor were scanned before and after administration of Bevacizumab. The average ADC from the monoexponential diffusion model did not change noticeably by post-treatment day 1. However, the biexponential model was found to be adequate for more voxels in the tumor and the product of perfusion fraction and pseudodiffusivity increased substantially in one day, suggesting the feasibility of using IVIM-DWI for early detection of vascular normalization.

                                   Tuesday 13:30-15:30                                                                          Computer 109           

13:30         4836.     Dynamic Contrast-Enhanced (DCE)-MRI Enhanced with Macromolecular Contrast Media for Monitoring Sorafenib Effect on Experimental Prostate Carcinomas

Clemens Christian Cyran1, Philipp Marius Paprottka1, Bettina Schwarz2, Steven Sourbron1, Olaf Dietrich1, Jobst von Einem1, Rabea Hinkel3, Christiane Bruns2, Hubertus Pietsch4, Maximilian F. Reiser1, Bernd J. Wintersperger1, Konstantin Nikolaou1

1Institute of Clinical Radiology, Munich University Hospitals - Campus Grosshadern, Munich, Germany; 2Department of Surgery, Munich University Hospitals - Campus Grosshadern, Munich, Germany; 3Department of Internal Medicine I, Munich University Hospitals - Campus Grosshadern, Munich, Germany; 4Contrast Media Research, Bayer Schering Pharma AG, Berlin, Germany

The purpose of this study was to investigate the effects of sorafenib on experimental prostate carcinomas in rats by dynamic MRI and macromolecular contrast media (MMCM) albumin-(Gd-DTPA). Target parameters were tumor endothelial permeability (ml/100ml/min) and tumor vascularity (%). In the therapy group treated daily with sorafenib (10mg/kg) tumor endothelial permeability and tumor vascularity decreased significantly (p<0.01) over one week. Results indicate a significant effect of sorafenib on experimental prostate carcinomas in rats. Tumor endothelial permeability and tumor vascularity as assayed with DCE-MRI and MMCM have the potential to be applied as non-invasive surrogate parameters of tumor response to anti-angiogenic therapy

14:00         4837.     Vessel Size Index MRI to Monitor the Effects of Vascular Disruption by ASA404 (Vadimezan, 5,6-Dimethylxanthenone-4-Acetic Acid) in Orthotopic Gliomas

Kirstie S. Opstad1, Simon P. Robinson2, Franklyn A. Howe1

1Division of Cardiac & Vascular Sciences, St. George's, University of London, London, United Kingdom; 2Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research, Sutton, United Kingdom

Vascular disrupting agents (VDAs) reduce tumour blood flow and non-invasive methods of monitoring are essential for brain tumours. Vessel size index (VSI) MRI was used to determine effects of the Tumour-VDA ASA404 (vadimezan, formerly AS1404, 5,6-dimethylxanthenone-4-acetic acid, DMXAA) on fractional blood volume (fBV) and blood vessel size (Rv) in orthotopic C6 gliomas. We show a post-treatment histogram shift towards reduced fBV and significant increase in fBV<0.4%, consistent with vascular collapse; and large post-ASA404 reductions in fBV and Rv indicate development of necrosis. In conclusion, VSI MRI appears effective in monitoring treatment effects of the Tumour-VDA ASA404 on brain tumour vasculature.

14:30         4838.     Detection and Improvement of Anti-Angiogenic Therapeutic Efficacy by Using Hemodynamic Response Imaging in Mice

Yifat Edrei1,2, Eitan Gross3, Nathalie Corchia1, Elia Dery1, Shmuel Ben-Sasson4, Rinat Abramovitch1,2

1The Goldyn Savad Inst. for Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel; 2MRI/MRS lab HBRC, Hadassah Hebrew University Medical Center, Jerusalem, Israel; 3Pediatric Surgery, Hadassah Hebrew University Medical Center; 4Experimental Medicine & Cancer Research, The Hebrew Universioty Hadassah Medical School

Since anti-angiogenic therapies may not lead to substantial tumor shrinkage, their effect is better imaged using perfusion imaging rather than tumor size measurement. Recently, we demonstrated the feasibility of Hemodynamic Response Imaging (HRI), an fMRI method combined with hypercapnia and hyperoxia, for monitoring changes in liver perfusion and hemodynamics. Here we show that a novel anti-angiogenic drug (Hamsa) reduces colorectal liver metastases growth and thus prolong mice survival. We assessed the therapeutic efficacy by HRI and revealed two types of response. By utilizing HRI we revealed the underlying mechanisim of Hamsa potential which hopefully would improve the Hamsa therapeutic potency.

15:00         4839.     In Vivo MRI Follow-Up of Murine Tumors Treated by Electrochemotherapy with Bleomycin.

Lucie Calmels1, Bassim Al-Sakere2,3, Lluis Mir2,3, Jean-Pierre Ruaud4, Anne Leroy-Willig4

1U2R2M, University Paris-Sud XI , Orsay, 91405, France; 2CNRS UMR 8121, Institut Gustave Roussy, Villejuif, 94805, France; 3UMR  8121, University Paris-Sud XI , Orsay, 91405; 4U2R2M, University Paris-Sud XI, Orsay, 91405, France

Sixteen mice bearing grafted fibrosarcoma were treated with electrotransfer without (E), after a low (B) and a high (HB) dose of bleomycin.Volume, ADC and T2 of tumors were measured before and after treatment. Bleomycin induced a volume decrease depending on the dose. ADC reached a maximum at 24 and 10 hrs for B and HB group respectively. T2 was increased during a few hours after application of electric field in the three groups.

                                   Wednesday 13:30-15:30                                                                     Computer 109           

13:30         4840.     Diffusion-Weighted Imaging for Rectal Cancer Response Monitoring After Neo-Adjuvant Radiochemotherapy: A Good Correlation with Pathological Response.

Martijn Intven1, Onne Reerink1, Taro Takahara2, Marielle E. P. Philippens1

1Radiation Oncology, University Medical Centre Utrecht, Utrecht, Netherlands; 2Radiology, University Medical Centre Utrecht, Utrecht, Netherlands

Rectal cancer response analysis after neo-adjuvant radiochemotherepy (RCT) is important because good pathological response prediction enables safe omission of surgery in the group of clinical complete responders. Diffusion-weighted MR imaging (DWI) reflects the microanatomy in tissues and is frequently used in oncology for tissue characterisation and response assessment.  In this study, we analysed rectal cancer response after neo-adjuvant RCT with DWI. Apparent diffusion coefficient (ADC) values were compared with the pathological rectal cancer regression grade. Unexpectedly, low post-RCT ADC values and low ADC differences correlated with a good pathological response after neo-adjuvant RCT.

14:00         4841.     Correlation of the Phospholipid-Related Signatures in 31P and 1H Spectra: An Approach to Increase the Sensitivity of the Prediction of Therapeutic Outcome in Non-Hodgkin's Lymphoma by In Vivo MRS

Fernando Arias-Mendoza1, Franklyn Howe2, Marion Stubbs3, Seung-Cheol Lee4, Geoffrey S. Payne5, Kristen Zakian6, Hamed Mojahed1, Harish Poptani4, Mary McLean3, Amita Shukla-Dave6, Nicholas R. Maisey5, Owen A. O'Connor7,8, Ruth Pettengell9, Steven J. Schuster4, David Cunningham10, John R. Griffiths3, Jerry D. Glickson4, Martin O. Leach5, Jason A. Koutcher6, Arend Heerschap11, Truman R. Brown1

1Radiology, Columbia University, New York, NY, United States; 2Radiology, St. George's Hospital, London, United Kingdom; 3Radiology, Cambridge University, Cambridge, United Kingdom; 4Radiology, University of Pennsylvania, Philadelphia, PA, United States; 5Radiology, Institute of Cancer Research, London, United Kingdom; 6Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States; 7Medical Oncology, Columbia University, New York, NY, United States; 8Medical Oncology, New York University, New York, NY, United States; 9Medical Oncology, St. George's Hospital, London, United Kingdom; 10Medical Oncology, Institute of Cancer Research, London, United Kingdom; 11Radiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands

In vivo localized, 31P and 1H MRS was acquired in tumors of non-Hodgkin’s lymphoma patients before treatment, and the phosphoethanolamine plus phosphocholine-to-nucleoside triphosphate and total choline-to-water ratios determined in the 31P and 1H tumor spectra respectively. In these preliminary data, the pretreatment ratios showed a linear correlation (y=0.16x 0.77, r2=0.7, p<0.005). This correlation and the increased sensitivity of 1H observations in comparison to those of 31P suggests that the prediction of therapeutic outcome by MR technology can be improved by the addition of 1H spectroscopy to the in vivo MR observations of NHL patients.

14:30         4842.     Dynamic Contrast-Enhanced MRI Parameters Monitor and Predict Outcome of Targeted Radionuclide Therapy in Patients with Neuroendocrine Tumour Liver Metastases

Keiko Miyazaki1, Matthew R. Orton1, James A. d'Arcy1, Val Lewington2, Martin O. Leach1, David J. Collins1, Dow-Mu Koh3

1CR-UK and EPSRC Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 2Department of Nuclear Medicine, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom; 3Department of Radiology, Royal Marsden NHS Foundation Trust, Sutton, Surrey, United Kingdom

Dynamic contrast-enhanced (DCE-) MRI is a technique that enables non-invasive interrogation of tissue microvascular environment. The role of quantitative DCE-MRI parameters in the assessment and prediction of response in patients with liver metastases to a targeted radionuclide therapy was investigated using both model-free and model-dependent data analyses. Distribution volume and IAUGC60 were found to be potential predictors of response. The number of fitted voxels and the enhancing fraction were found to be most sensitive in assessing treatment response. This study demonstrates the role of DCE-MRI as a potential biomarker for predicting and assessing treatment response.

15:00         4843.     Diffusion Weighted MRI for Assessing Treatment Response in Myeloma Bone Disease - not available

Christina Messiou1, David Collins1, Veronica Morgan1, Sharon Giles1, Catherine Parry-Jones1, Faith Davies2, Gareth Morgan3, Nandita deSouza1

1CRUK and EPSRC Cancer Imaging Centre, Department of Magnetic Resonace Imaging, Institute of Cancer Research/The Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 2Molecular Target Treatment Team, Institute of Cancer Research/The Royal Marsden Hospital, Sutton, Surrey, United Kingdom; 3Leukaemia and Molecular Genetics Team, Institute of Cancer Research/The Royal Marsden Hospital, Sutton, Surrey, United Kingdom

There is growing interest in diffusion weighted (DW) MRI as a biomarker of treatment response in metastatic and myeloma bone disease. We performed an ROC analysis of normal vs myeloma involved marrow. Using an ADC threshold of 724 mm2s-1 x 10-6 the sensitivity and specificity for detecting myeloma marrow involvement are 90 and 70% respectively. This threshold was applied to a test case to produce segmented ADC maps which were used to predict treatment response.

                                   Thursday 13:30-15:30                                                                        Computer 109           

13:30         4844.     Monitoring Treatment Response of Prostate Cancer Bone Metastases with the Functional Diffusion Map

Carolin Reischauer1, Johannes M. Froehlich2, Christoph A. Binkert2, Peter Boesiger1, Andreas Gutzeit2

1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland; 2Department of Radiology, Cantonal Hospital Winterthur, Winterthur, Switzerland

Most patients with advanced prostate cancer feature bone metastases that are incurable. Thus, novel therapies are constantly developed for which treatment success has to be assessed. The present work demonstrates, in a prospective clinical study of patients with known skeletal metastases, that the functional diffusion map (fDM) allows monitoring treatment response. Thereby, the fDM segments the tumor into three regions with significantly increased, significantly decreased, and unchanged apparent diffusion coefficients (ADCs). In the present study large regions with significantly increased ADCs were observed under therapy indicating treatment success. Furthermore, the spatial distribution of tumor response could be successfully derived.

14:00         4845.     DCE-MRI Demonstrates Antivascular Properties of Sorafenib in Metastatic Hormone-Resistant Prostate Cancer

Mark Alan Rosen1, Ganesh Adluru1, Ravi Amaravadi2, Yiqun Xue1, Yu Jiangsheng1, Hee-Kwon Song1, Naomi Haas2, Peter O'Dwyer2

1Radiology, University of Pennsylvania, Philadelphia, PA, United States; 2Medicine, University of Pennsylvania, Philadelphia, PA, United States

DCE-MRI using large-volume radial imaging was used to gauge response of metastatic prostate cancer to combination therapy including the anti-angiogenic agent, sorafenib.  We observed strong anti-vascular response of tumors to a seven-day course of sorafenib.  This effect was reversed on follow-up DCE-MRI at day 21, after a mandated three-day sorafenib free-interval, suggesting that the sorafenib effects on tumor were rapidly reversible.  We also noted that alterations in tumor vascularity, as reflected in changes in tumor AUC60, were negatively correlated with early changes in serum PSA levels, in concert with clinical results revealing sorafenib’s potential to increase PSA levels.

 

15:00         4846.     The Assessment of Early Vascular Effects of the Angiogenesis Inhibitor Sunitinib in Renal Cell Carcinoma (RCC) by DCE-MRI and Diffusion Weight MRI (DWI) at 3 Tesla.

Ingrid Desar1, H. W.M. van Laarhoven1, T. Hambrock2, E. G.W. ter Voert2, J. J.A. van Asten2, D.J. van Spronsen3, J. O. Barentsz2, P. F.A. Mulders4, A. Heerschap2, Carla M.L. van Herpen1

1Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; 2Radiology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands; 3Medical Oncology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands; 4Urology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands

Sunitinib is an oral angiogenesis inhibitor, used as first line treatment in patients with metastatic renal cell cancer (RCC). A successful antiangiogenic treatment is expected to result in stabilization of the vasculature, a reduction in permeability and in interstitial fluid pressure, and the development of necrosis. This study aims to assess the early vascular effects of sunitinib in RCC patients with a DCE-MRI and DWI at 3T. Treatment with sunitinib provokes significant increases in ADC after 3 days, with recurrence to baseline values at day 10. This is possibly due to the development of edema and necrosis. In this limited number of patients, no significant changes in both mean kep and Ktrans values, as well as in the histogram results were found, although in individual patients some trends indicative for early vascular effects of sunitinib were observed.