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Improving the prevention and detection of preinvasive ductal carcinoma in situ (DCIS) is expected to lower both morbidity and mortality from breast cancer. Transgenic mouse models can be used as a ‘test bed’ to develop new imaging methods and to evaluate the efficacy of candidate preventive therapies. We hypothesized that despite its microscopic size, early murine mammary cancer, including DCIS, might be accurately detected by MRI. C3(1) SV40 TAg female mice (n = 23) between 10 and 18 weeks of age were selected for study. Eleven mice were subjected to in vitro imaging using a T2-weighted spin echo sequence and 12 mice were selected for in vivo imaging using a T1-weighted gradient echo, a T2-weighted spin echo and high spectral and spatial resolution imaging sequences. The imaged glands were carefully dissected, formalin fixed and paraffin embedded, and then H&E stained sections were obtained. The ratio of image-detected versus histologically detected cancers was obtained by reviewing the MR images and H&E sections independently and using histology as the gold standard. MR images were able to detect 12/12 intramammary lymph nodes, 1/1 relatively large (∼5 mm) tumor, 17/18 small (∼1 mm) tumors and 13/16 ducts distended with DCIS greater than 300 µm. Significantly, there were no false positives—i.e., image detection always corresponded to a histologically detectable cancer in this model. These results indicate that MR imaging can reliably detect both preinvasive in situ and early invasive mammary cancers in mice with high sensitivity. This technology is an important step toward the more effective use of non-invasive imaging in pre-clinical studies of breast cancer prevention, detection and treatment. [ABSTRACT FROM AUTHOR]

Purpose: The interpretation of prostate multiparametric magnetic resonance imaging (MRI) is subjective in nature, and there is large inter-observer variability among radiologists and up to 30% of clinically significant cancers are missed. This has motivated the development of new MRI techniques and sequences, especially quantitative approaches to improve prostate cancer diagnosis. Using hybrid multidimensional MRI, apparent diffusion coefficient (ADC) and T2 have been shown to change as a function of echo time (TE) and b-values, and that this dependence is different for cancer and benign tissue, which can be exploited for prostate cancer diagnosis. The purpose of this study is to investigate whether four-quadrant vector mapping of hybrid multidimensional MRI (HM-MRI) data can be used to diagnose prostate cancer (PCa) and determine cancer aggressiveness., Methods: Twenty-one patients with confirmed PCa underwent preoperative MRI prior to radical prostatectomy. Axial HM-MRI were acquired with all combinations of TE = 47, 75, 100 ms and b-values of 0, 750, 1500 s/mm 2 , resulting in a 3 × 3 data matrix associated with each voxel. Prostate Quadrant (PQ) mapping analysis represents HM-MRI data for each voxel as a color-coded vector in the four-quadrant space of HM-MRI parameters (a 2D matrix of signal values for each combination of b-value and TE) with associated amplitude and angle information representing the change in T2 and ADC as a function of b-value and TE, respectively., Results: Cancers have a higher PQ4 (22.50% ± 21.27%) and lower PQ2 (69.86% ± 28.24%) compared to benign tissue: peripheral, transition, and central zone (PQ4 = 0.13% ± 0.56%, 5.73% ± 15.07%, 2.66% ± 4.05%, and PQ2 = 98.51% ± 3.05%, 86.18% ± 21.75%, 93.38% ± 9.88%, respectively). Cancers have a higher vector angle (206.5 ± 41.8°) and amplitude (0.017 ± 0.013) compared to benign tissue. PQ metrics showed moderate correlation with Gleason score (|ρ| = 0.388-0.609), with more aggressive cancers being associated with increased PQ4 and angle and reduced PQ2 and amplitude. A combination of four-quadrant analysis metrics provided an area under the curve of 0.904 (p < 0.001) for the differentiation of prostate cancer from benign prostatic tissue., Conclusions: Four-quadrant vector mapping of HM-MRI data provides effective cancer markers, with cancers associated with high PQ4 and high vector angle and lower PQ2 and vector amplitude., (© 2023 American Association of Physicists in Medicine.)

We propose a general method for combining multiple models to predict tissue microstructure, with an exemplar using in vivo diffusion-relaxation MRI data. The proposed method obviates the need to select a single 'optimum' structure model for data analysis in heterogeneous tissues where the best model varies according to local environment. We break signal interpretation into a three-stage sequence: (1) application of multiple semi-phenomenological models to predict the physical properties of tissue water pools contributing to the observed signal; (2) from each Stage-1 semi-phenomenological model, application of a tissue microstructure model to predict the relative volumes of tissue structure components that make up each water pool; and (3) aggregation of the predictions of tissue structure, with weightings based on model likelihood and fractional volumes of the water pools from Stage-1. The multiple model approach is expected to reduce prediction variance in tissue regions where a complex model is overparameterised, and bias where a model is underparameterised. The separation of signal characterisation (Stage-1) from biological assignment (Stage-2) enables alternative biological interpretations of the observed physical properties of the system, by application of different tissue structure models. The proposed method is exemplified with human prostate diffusion-relaxation MRI data, but has potential application to a wide range of analyses where a single model may not be optimal throughout the sampled domain., (© 2023. Springer Nature Limited.)

Purpose: Compare reader performance when adding the Hybrid Multidimensional-MRI (HM-MRI) map to multiparametric MRI (mpMRI+HM-MRI) versus mpMRI alone and inter-reader agreement in diagnosing clinically significant prostate cancers (CSPCa)., Methods: All 61 patients who underwent mpMRI (T2-, diffusion-weighted (DWI), and contrast-enhanced scans) and HM-MRI (with multiple TE/b-value combinations) before prostatectomy or MRI-fused-transrectal ultrasound-guided biopsy between August, 2012 and February, 2020, were retrospectively analyzed. Two experienced readers (R1, R2) and two less-experienced readers (less than 6-year MRI prostate experience) (R3, R4) interpreted mpMRI without/with HM-MRI in the same sitting. Readers recorded the PI-RADS 3-5 score, lesion location, and change in score after adding HM-MRI. Each radiologist's mpMRI+HM-MRI and mpMRI performance measures (AUC, sensitivity, specificity, PPV, NPV, and accuracy) based on pathology, and Fleiss' kappa inter-reader agreement was calculated and compared., Results: Per-sextant R3 and R4 mpMRI+HM-MRI accuracy (82% 81% vs. 77%, 71%; p=.006, <.001) and specificity (89%, 88% vs. 84%, 75%; p=.009, <.001) were higher than with mpMRI. Per-patient R4 mpMRI+HM-MRI specificity improved (48% from 7%; p<.001). R1 and R2 mpMRI+HM-MRI specificity per-sextant (80%, 93% vs. 81%, 93%; p=.51,>.99) and per-patient (37%, 41% vs. 48%, 37%; p=.16, .57) remained similar to mpMRI. R1 and R2 per-patient AUC with mpMRI+HM-MRI (0.63, 0.64 vs. 0.67, 0.61; p=.33, .36) remained similar to mpMRI, but R3 and R4 mpMRI+HM-MRI AUC (0.73, 0.62) approached R1 and R2 AUC. Per-patient inter-reader agreement, mpMRI+HM-MRI Fleiss Kappa, was higher than mpMRI (0.36 [95% CI 0.26, 0.46] vs. 0.17 [95% CI 0.07, 0.27]); p=.009)., Conclusion: Adding HM-MRI to mpMRI (mpMRI+HM-MRI) improved specificity and accuracy for less-experienced readers, improving overall inter-reader agreement., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To identify the optimal threshold in 18 F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO 2 EPRI) as ground truth for hypoxia, defined by pO 2 [Formula: see text] 10 mmHg., Methods: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue. Dynamic contrast enhanced (DCE) MRI parametric images of K trans and v e were generated to model tumor vascular properties. Images from PET/EPR/MRI were co-registered and resampled to isotropic 0.5 mm voxel resolution for analysis. PET images were converted to standardized uptake value (SUV) and tumor-to-muscle ratio (TMR) units. FMISO uptake thresholds were evaluated using receiver operating characteristic (ROC) curve analysis to find the optimal FMISO threshold and unit with maximum overall hypoxia similarity (OHS) with pO 2 EPRI, where OHS = 1 shows perfect overlap and OHS = 0 shows no overlap. The means of dice similarity coefficient, normalized Hausdorff distance, and accuracy were used to define the OHS. Monotonic relationships between EPRI/PET/DCE-MRI were evaluated with the Spearman correlation coefficient ([Formula: see text]) to quantify association of vasculature on hypoxia imaged with both FMISO PET and pO 2 EPRI., Results: FMISO PET thresholds to define hypoxia with maximum OHS (both OHS = 0.728 [Formula: see text] 0.2) were SUV [Formula: see text] 1.4 [Formula: see text] SUV mean and SUV [Formula: see text] 0.6 [Formula: see text] SUV max . Weak-to-moderate correlations (|[Formula: see text]|< 0.70) were observed between PET/EPRI hypoxia images with vascular permeability (K trans ) or fractional extracellular-extravascular space (v e ) from DCE-MRI., Conclusion: This is the first in vivo comparison of FMISO uptake with pO 2 EPRI to identify the optimal FMISO threshold to define tumor hypoxia, which may successfully direct hypoxic tumor boosts in patients, thereby enhancing tumor control., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Radiomic features extracted from breast lesion images have shown potential in diagnosis and prognosis of breast cancer. As medical centers transition from 1.5 T to 3.0 T magnetic resonance (MR) imaging, it is beneficial to identify potentially robust radiomic features across field strengths because images acquired at different field strengths could be used in machine learning models. Dynamic contrast-enhanced MR images of benign breast lesions and hormone receptor positive/HER2-negative (HR+/HER2-) breast cancers were acquired retrospectively, yielding 612 unique cases: 150 and 99 benign lesions imaged at 1.5 T and 3.0 T, and 223 and 140 HR+/HER2- cancerous lesions imaged at 1.5 T and 3.0 T, respectively. In addition, an independent set of seven lesions imaged at both field strengths, three benign lesions and four HR+/HER2- cancers, was analyzed separately. Lesions were automatically segmented using a 4D fuzzy c-means method; thirty-eight radiomic features were extracted. Feature value distributions were compared by cancer status and imaging field strength using the Kolmogorov-Smirnov test. Features that did not demonstrate a statistically significant difference were considered to be potentially robust. The area under the receiver operating characteristic curve (AUC), for the task of classifying lesions as benign or HR+/HER2- cancer, was determined for each feature at each field strength. Three features were found to be both potentially robust across field strength and of high classification performance, i.e., AUCs statistically greater than 0.5 in the classification task: one shape feature (irregularity), one texture feature (sum average) and one enhancement variance kinetics features (enhancement variance increasing rate). In the demonstration set of lesions imaged at both field strengths, two of the three potentially robust features showed qualitative agreement across field strength. These findings may contribute to the development of computer-aided diagnosis models that are robust across field strength for this classification task., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To enhance the spatial accuracy of fluorine 18 ( 18 F) misonidazole (MISO) PET imaging of hypoxia by using dynamic contrast-enhanced (DCE) MR images as a basis for modifying PET images and by using electron paramagnetic resonance (EPR) partial oxygen pressure (pO 2 ) as the reference standard., Materials and Methods: Mice ( n = 10) with leg-borne MCa4 mammary carcinomas underwent EPR imaging, T2-weighted and DCE MRI, and 18 F-MISO PET/CT. Images were registered to the same space for analysis. The thresholds of hypoxia for PET and EPR images were tumor-to-muscle ratios greater than or equal to 2.2 mm Hg and less than or equal to 14 mm Hg, respectively. The Dice similarity coefficient (DSC) and Hausdorff distance (d H ) were used to quantify the three-dimensional overlap of hypoxia between pO 2 EPR and 18 F-MISO PET images. A training subset ( n = 6) was used to calculate optimal DCE MRI weighting coefficients to relate EPR to the PET signal; the group average weights were then applied to all tumors (from six training mice and four test mice). The DSC and d H were calculated before and after DCE MRI-corrected PET images were obtained to quantify the improvement in overlap with EPR pO 2 images for measuring tumor hypoxia., Results: The means and standard deviations of the DSC and d H between hypoxic regions in original PET and EPR images were 0.35 mm ± 0.23 and 5.70 mm ± 1.7, respectively, for images of all 10 mice. After implementing a preliminary DCE MRI correction to PET data, the DSC increased to 0.86 mm ± 0.18 and the d H decreased to 2.29 mm ± 0.70, showing significant improvement ( P < .001) for images of all 10 mice. Specifically, for images of the four independent test mice, the DSC improved with correction from 0.19 ± 0.28 to 0.80 ± 0.29 ( P = .02), and the d H improved from 6.40 mm ± 2.5 to 1.95 mm ± 0.63 ( P = .01)., Conclusion: Using EPR information as a reference standard, DCE MRI information can be used to correct 18 F-MISO PET information to more accurately reflect areas of hypoxia. Keywords: Animal Studies, Molecular Imaging, Molecular Imaging-Cancer, PET/CT, MR-Dynamic Contrast Enhanced, MR-Imaging, PET/MR, Breast, Oncology, Tumor Mircoenvironment, Electron Paramagnetic Resonance Supplemental material is available for this article. © RSNA, 2021., Competing Interests: Disclosures of Conflicts of Interest: I.G. disclosed no relevant relationships. B.E. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: co-owner of O2M Technologies, a company that fabricates EPR imaging instruments. No O2M instruments, IP, or technology was used in the present work. E.B. disclosed no relevant relationships. L.L. disclosed no relevant relationships. E.M. disclosed no relevant relationships. H.M.T. disclosed no relevant relationships. X.F. disclosed no relevant relationships. M.G. disclosed no relevant relationships. D.B. Activities related to the present article: National Cancer Institute grant R01CA236385 was used to partially fund the author’s salary for this project. Activities not related to the present article: money from O2M Technologies paid was part of the author’s transition to employment with O2M. These funds were not a part of the relevant work. Other relationships: disclosed no relevant relationships. M.Z. disclosed no relevant relationships. S.S. disclosed no relevant relationships. H.K. disclosed no relevant relationships. R.F. disclosed no relevant relationships. M.B. disclosed no relevant relationships. A.K. disclosed no relevant relationships. G.K. disclosed no relevant relationships. C.M.K. disclosed no relevant relationships. H.H. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: disclosed no relevant relationships. Other relationships: Inventor of several patents, including Magnetic Resonance Analysis of Substances in Samples that Include Dissipative Material (inventor: Howard Halpern; patent no.: 4,714,886); Selective Isotopic Labelling of Spin Labels for Electron Resonance Spectroscopy (inventors: Howard Halpern, Beverly A. Teicher; patent no.: 5,431,901) Imaging system performing substantially exact reconstruction and using non-traditional trajectories (inventors: Pan X, Zou, Yu, Yu L, Kao; C-M, King M, Giger M, Xia D, Halpern H, Pelizzari C, Sidky E, Cho S; patent no: 7,444,011); High isolation transmit/receive surface coils and method for EPRI (inventor: Halpern H; patent no. 8,644,955); T1-Senstivie inversion recovery-imaging method and apparatus for EPRI (inventors: Halpern H, Epel B; patent no.: 9,392,957); Method and apparatus for resonator signal production and measurement (inventors: Halpern H, Sundramoorthy S, Epel B; patent no.:10,551,450B2); Method and high isolation transmit/receive surface coils for EPRI (inventor: Howard J. Halpern; patent no.: 10,568,537); and Alderman-Grant/Loop-Gap High Isolation Crossed Field Bimodal Resonator (inventors: Halpern H, Epel B, Sundramoorthy S; submitted: 4/12/2011). C.T.C. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: royalties and stock options from RefleXion Medical, which is licensed from the University of Chicago for the author’s patent on PET or SPECT-guided radiation therapy. Other relationships: disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Background: Focal laser ablation (FLA) is a minimally invasive thermal ablation, guided by MRI through an optical fiber, to induce coagulative necrosis in cancer., Purpose: To evaluate the feasibility of high spectral and spatial resolution imaging using multiecho gradient echo (MEGE) MRI for identification of ablation zones, after FLA of prostate cancers., Study Type: Prospective., Population: Fourteen patients with biopsy-confirmed localized prostate cancers., Field Strength/sequence: FLA was performed under monitored conscious sedation with a 1.5T MRI scanner. Axial MEGE images were acquired before and after the last FLA. Pre- and postcontrast enhanced T 1 -weighted (pT 1 W) images were acquired to assess the FLA zone as a reference standard., Assessment: The T 2 * maps and water resonance peak height (WPH) images were calculated from the MEGE data. Ablation area was outlined using an active contour method. The maximum ablation area and total ablation volume were calculated from T 2 * and WPH images, and compared with the sizes measured from pT 1 W images., Statistical Tests: Nonparametric Kruskal-Wallis tests were performed to determine whether there was significant difference in calculated ablation areas and volumes between T 2 * , WPH, and pT 1 W images., Results: Average T 2 * (38.9 ± 14.1 msec) in the ablation area was significantly shorter (P = 0.03) than the preablation area T 2 * (57.8 ± 25.3 msec). The normalized WPH value over the ablation area (1.3 ± 0.6) was significantly decreased (P = 0.02) more than the preablation area (2.0 ± 0.9). The maximum ablation areas measured by T 2 * (295.7 ± 96.4 mm 2 ), WPH (312.2 ± 63.0 mm 2 ), and pT 1 W (320.3 ± 82.9 mm 2 ) images were all similar. Furthermore, there was no significant difference (P = 0.31) for measured ablation volumes 3310.5 ± 649.5, 3406.4 ± 684.9, and 3672.5 ± 832.4 mm 3 between T 2 * , WPH, and pT 1 W images, respectively. DATA CONCLUSION: T 2 * and WPH images provide acceptable measurements of ablation zones during FLA treatment of prostate cancers without the need for contrast agent injection. This might allow repeated assessment following each heating period so that subsequent ablations can be optimized., Level of Evidence: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;49:1374-1380., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer. Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene., Results: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1 , 61 BRCA2 ); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1 , 3 BRCA2 , 1 CDH1 ). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non- BRCA1/2 carriers, respectively., Conclusions: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693., (©2018 American Association for Cancer Research.)

Objective: The purpose of this study is to describe the quantitative and qualitative findings of multiparametric prostate MRI performed after MRI-guided focal laser ablation of prostate cancer., Materials and Methods: A total of 27 consenting patients met the study inclusion criteria, which included but were not limited to the presence of clinical category T1c-T2a prostate cancer with a Gleason score of 7 or less, having undergone prostate biopsy before and after focal laser ablation, and having undergone MRI before ablation, immediately after ablation, and 3 and 12 months after ablation. Signal changes were evaluated both qualitatively and quantitatively and were then correlated with the results of subsequent biopsy performed at 3 and 12 months after ablation., Results: MRI performed immediately after ablation revealed a hypovascular defect in the ablation zone, with patchy or bandlike decreased T2 signal most commonly noted at 3 months (in 66.7% of ablated lesions) and T2 scarring observed in most lesions (66.7%) at 12 months. Patchy or bandlike decreased apparent diffusion coefficient signal and scarlike changes were most prevalent at 3 months after ablation (50.0% of lesions), and these features remained the most commonly observed findings at 12 months after ablation (27.8% of lesions). At 12 months after ablation, 10 patients were found to have recurrent tumor, with three patients found to have persistent cancer when biopsy was performed at the ablation site. All postablation biopsy cases with positive results showed suspicious T2 and apparent diffusion coefficient characteristics, which were considered to be a well-defined nodular intermediate signal on both of these sequences. Two of the patients for whom positive biopsy findings were noted had focal enhancement of the ablation zone. A significant reduction in the forward volume transfer constant after ablation was found at the ablation site on follow-up examination., Conclusion: Multiparametric MRI can reveal postablation changes in the prostate and can be a valuable tool for monitoring patients who have undergone MRI-guided focal laser ablation.

Urinary complications resulting from benign prostatic hyperplasia and bladder outlet obstruction continue to be a serious health problem. Novel animal model systems and imaging approaches are needed to understand the mechanisms of disease initiation, and to develop novel therapies for benign prostatic hyperplasia. Long-term administration of both estradiol and testosterone in mice can result in prostatic enlargement and recapitulate several clinical components of lower urinary tract symptoms. Herein, we use longitudinal magnetic resonance imaging and histological analyses to quantify changes in prostatic volume, urethral volume, and genitourinary vascularization over time in response to estradiol-induced prostatic enlargement. Our data demonstrate significant prostatic enlargement by 12 weeks after treatment, with no detectable immune infiltration by macrophages or T- or B-cell populations. Importantly, the percentage of cell death, as measured by terminal deoxynucleotidyl transferase dUTP nick-end labeling, was significantly decreased in the prostatic epithelium of treated animals as compared to controls. We found no significant change in prostate cell proliferation in treated mice when compared to controls. These studies highlight the utility of magnetic resonance imaging to quantify changes in prostatic and urethral volumes over time. In conjunction with histological analyses, this approach has the high potential to enable mechanistic studies of initiation and progression of clinically relevant lower urinary tract symptoms. In addition, this model is tractable for investigation and testing of therapeutic interventions to ameliorate or potentially reverse prostatic enlargement., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of our study was to evaluate the role of a hybrid T2-weighted imaging-DWI sequence for prostate cancer diagnosis and differentiation of aggressive prostate cancer from nonaggressive prostate cancer., Materials and Methods: Twenty-one patients with prostate cancer who underwent preoperative 3-T MRI and prostatectomy were included in this study. Patients underwent a hybrid T2-weighted imaging-DWI examination consisting of DW images acquired with TEs of 47, 75, and 100 ms and b values of 0 and 750 s/mm(2). The apparent diffusion coefficient (ADC) and T2 were calculated for cancer and normal prostate ROIs at each TE and b value. Changes in ADC and T2 as a function of increasing the TE and b value, respectively, were analyzed. A new metric termed "PQ4" was defined as the percentage of voxels within an ROI that has increasing T2 with increasing b value and has decreasing ADC with increasing TE., Results: ADC values were significantly higher in normal ROIs than in cancer ROIs at all TEs (p < 0.0001). With increasing TE, the mean ADC increased 3% in cancer ROIs and increased 12% in normal ROIs. T2 was significantly higher in normal ROIs than in cancer ROIs at both b values (p ≤ 0.0002). The mean T2 decreased with increasing b value in cancer ROIs (ΔT2 = -17 ms) and normal ROIs (ΔT2 = -52 ms). PQ4 clearly differentiated normal ROIs from prostate cancer ROIs (p = 0.0004) and showed significant correlation with Gleason score (ρ = 0.508, p < 0.0001)., Conclusion: Hybrid MRI measures the response of ADC and T2 to changing TEs and b values, respectively. This approach shows promise for detecting prostate cancer and determining its aggressiveness noninvasively.

Aim: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer., Methods: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy., Results: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum., Conclusion: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy.

Purpose: The purpose of the study is to determine short-term reproducibility of apparent diffusion coefficient (ADC) estimated from diffusion-weighted magnetic resonance (DW-MR) imaging of the prostate., Methods: Fourteen patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Each patient underwent two, consecutive and identical DW-MR scans on a 3T system. ADC values were calculated from each scan and a deformable registration was performed to align corresponding images. The prostate and cancerous regions of interest (ROIs) were independently analyzed by two radiologists. The prostate volume was analyzed by sextant. Per-voxel absolute and relative percentage variations in ADC were compared between sextants. Per-voxel and per-ROI variations in ADC were calculated for cancerous ROIs., Results: Per-voxel absolute difference in ADC in the prostate ranged from 0 to 1.60 × 10(-3) mm(2)/s (per-voxel relative difference 0% to 200%, mean 10.5%). Variation in ADC was largest in the posterior apex (0% to 200%, mean 11.6%). Difference in ADC variation between sextants was not statistically significant. Cancer ROIs' per-voxel variation in ADC ranged from 0.001 × 10(-3) to 0.841 × 10(-3) mm(2)/s (0% to 67.4%, mean 11.2%) and per-ROI variation ranged from 0 to 0.463 × 10(-3) mm(2)/s (mean 0.122 × 10(-3) mm(2)/s)., Conclusions: Variation in ADC within the human prostate is reasonably small, and is on the order of 10%.

Rationale and Objectives: Evaluate qualitative dynamic contrast-enhanced magnetic resonance imaging (MRI) characteristics of normal central zone based on recently described central zone MRI features., Materials and Methods: Institutional review board-approved, Health Insurance Portability and Accountability Act compliant study, 59 patients with prostate cancer, histopathology proven to not involve central zone or prostate base, underwent endorectal MRI before prostatectomy. Two readers independently reviewed T2-weighted images and apparent diffusion coefficient (ADC) maps identifying normal central zone based on low signal intensity and location. Next, two readers drew bilateral central zone regions of interest on dynamic contrast-enhanced magnetic resonance images in consensus and independently recorded enhancement curve types as type 1 (progressive), type 2 (plateau), and type 3 (wash-out). Identification rates of normal central zone and enhancement curve type were recorded and compared for each reviewer. The institutional review board waiver was approved and granted 05/2010., Results: Central zone identified in 92%-93% of patients on T2-weighted images and 78%-88% on ADC maps without significant difference between identification rates (P = .63 and P = .15 and inter-reader agreement (κ) is 0.64 and 0.29, for T2-weighted images and ADC maps, respectively). All central zones were rated either curve type 1 or curve type 2 by both radiologists. No statistically significant difference between the two radiologists (P = .19) and inter-reader agreement was κ = 0.37., Conclusions: Normal central zone demonstrates either type 1 (progressive) or type 2 (plateau) enhancement curves on dynamic contrast-enhanced MRI that can be potentially useful to differentiate central zone from prostate cancer that classically demonstrates a type 3 (wash-out) enhancement curve., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the performance of computer-aided diagnosis (CADx) analysis of precontrast high spectral and spatial resolution (HiSS) MRI to that of clinical dynamic contrast-enhanced MRI (DCE-MRI) in the diagnostic classification of breast lesions., Materials and Methods: Thirty-four malignant and seven benign lesions were scanned using two-dimensional (2D) HiSS and clinical 4D DCE-MRI protocols. Lesions were automatically segmented. Morphological features were calculated for HiSS, whereas both morphological and kinetic features were calculated for DCE-MRI. After stepwise feature selection, Bayesian artificial neural networks merged selected features, and receiver operating characteristic (ROC) analysis evaluated the performance with leave-one-lesion-out validation., Results: AUC (area under the ROC curve) values of 0.92 ± 0.06 and 0.90 ± 0.05 were obtained using CADx on HiSS and DCE-MRI, respectively, in the task of classifying benign and malignant lesions. While we failed to show that the higher HiSS performance was significantly better than DCE-MRI, noninferiority testing confirmed that HiSS was not worse than DCE-MRI., Conclusion: CADx of HiSS (without contrast) performed similarly to CADx on clinical DCE-MRI; thus, computerized analysis of HiSS may provide sufficient information for diagnostic classification. The results are clinically important for patients in whom contrast agent is contra-indicated. Even in the limited acquisition mode of 2D single slice HiSS, by using quantitative image analysis to extract characteristics from the HiSS images, similar performance levels were obtained as compared with those from current clinical 4D DCE-MRI. As HiSS acquisitions become possible in 3D, CADx methods can also be applied. Because HiSS and DCE-MRI are based on different contrast mechanisms, the use of the two protocols in combination may increase diagnostic accuracy., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: The purpose of this article is to study relationships between MRI-based prostate volume and volume-adjusted serum prostate-specific antigen (PSA) concentration estimates and prostate cancer Gleason score., Materials and Methods: The study included 61 patients with prostate cancer (average age, 63.3 years; range 52-75 years) who underwent MRI before prostatectomy. A semiautomated and MRI-based technique was used to estimate total and central gland prostate volumes, central gland volume fraction (central gland volume divided by total prostate volume), PSA density (PSAD; PSA divided by total prostate volume), and PSAD for the central gland (PSA divided by central gland volume). These MRI-based volume and volume-adjusted PSA estimates were compared with prostatectomy specimen weight and Gleason score by using Pearson (r) or Spearman (ρ) correlation coefficients., Results: The estimated total prostate volume showed a high correlation with reference standard volume (r = 0.94). Of the 61 patients, eight (13.1%) had a Gleason score of 6, 40 (65.6%) had a Gleason score of 7, seven (11.5%) had a Gleason score of 8, and six (9.8%) had a Gleason score of 9 for prostate cancer. The Gleason score was significantly correlated with central gland volume fraction (ρ = -0.42; p = 0.0007), PSAD (ρ = 0.46; p = 0.0002), and PSAD for the central gland (ρ = 0.55; p = 0.00001)., Conclusion: Central gland volume fraction, PSAD, and PSAD for the central gland estimated from MRI examinations show a modest but significant correlation with Gleason score and have the potential to contribute to personalized risk assessment for significant prostate cancer.

Purpose: To evaluate the feasibility and safety of magnetic resonance (MR) imaging-guided laser-based thermotherapy in men with clinically low-risk prostate cancer and a concordant lesion at biopsy and MR imaging., Materials and Methods: This HIPAA-compliant phase I prospective study was approved by the institutional review board. Informed consent was obtained from all patients. Transperineal MR imaging-guided focal laser ablation for clinically low-risk prostate cancer was performed in patients with a Gleason score of 7 or less in three or fewer cores limited to one sextant obtained with transrectal ultrasonography (US)-guided biopsy and a concordant lesion at MR imaging. Lesions were targeted with a laser ablation system. Periprocedural complications were recorded. The International Prostate Symptom Score (IPSS) and the Sexual Health Inventory for Men (SHIM) score were collected before and after the procedure. MR imaging-guided biopsy of the ablation zone was performed 6 months after treatment. The prostate-specific antigen level, IPSS, and SHIM score before and after ablation were compared by using the Wilcoxon signed rank test., Results: Treatment was successfully completed in nine patients (procedure duration, 2.5-4 hours; mean laser ablation duration, 4.3 minutes). Immediate contrast-enhanced posttreatment MR imaging showed a hypovascular defect in eight patients. Self-resolving perineal abrasion and focal paresthesia of the glans penis each occurred in one patient. The mean (± standard deviation) IPSS and SHIM score at baseline were 5.8 ± 5.3 and 19.0 ± 8.0, respectively. Average score changes were not significantly different from zero during follow-up (P = .18-.99). MR imaging-guided biopsy of the ablation zone showed no cancer in seven patients (78%) and Gleason grade 6 cancer in two (22%)., Conclusion: Transperineal MR imaging-guided focal laser ablation appears to be a feasible and safe focal therapy option for clinically low-risk prostate cancer.

Sorafenib is a multi-kinase inhibitor that blocks cell proliferation and angiogenesis. It is currently approved for advanced hepatocellular and renal cell carcinomas in humans, where its major mechanism of action is thought to be through inhibition of vascular endothelial growth factor and platelet-derived growth factor receptors. The purpose of this study was to determine whether pixel-by-pixel analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is better able to capture the heterogeneous response of Sorafenib in a murine model of colorectal tumor xenografts (as compared with region of interest analysis). MRI was performed on a 9.4 T pre-clinical scanner on the initial treatment day. Then either vehicle or drug were gavaged daily (3 days) up to the final image. Four days later, the mice were again imaged. The two-compartment model and reference tissue method of DCE-MRI were used to analyze the data. The results demonstrated that the contrast agent distribution rate constant (K(trans)) were significantly reduced (p < 0.005) at day-4 of Sorafenib treatment. In addition, the K(trans) of nearby muscle was also reduced after Sorafenib treatment. The pixel-by-pixel analysis (compared to region of interest analysis) was better able to capture the heterogeneity of the tumor and the decrease in K(trans) four days after treatment. For both methods, the volume of the extravascular extracellular space did not change significantly after treatment. These results confirm that parameters such as K(trans), could provide a non-invasive biomarker to assess the response to anti-angiogenic therapies such as Sorafenib, but that the heterogeneity of response across a tumor requires a more detailed analysis than has typically been undertaken.

Aim: To evaluate the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) findings of bone metastasis in prostate cancer patients., Methods: Sixteen men with a diagnosis of metastatic prostate cancer to bones were examined with DCE-MRI at 1.5 Tesla. The mean contrast agent concentration vs time curves for bone metastasis and normal bone were calculated and K(trans) and ve values were estimated and compared., Results: An early significant enhancement (wash-out: n = 6, plateau: n = 8 and persistent: n = 2) was detected in all bone metastases (n = 16). Bone metastasis from prostate cancer showed significant enhancement and high K(trans) and ve values compared to normal bone which does not enhance in the elderly population. The mean K(trans) was 0.101/min and 0.0051/min (P < 0.001), the mean ve was 0.141 and 0.0038 (P < 0.001), for bone metastases and normal bone, respectively., Conclusion: DCE-MRI and its quantitative perfusion parameters may have a role in improving the detection of skeletal metastasis in prostate cancer patients.

Purpose: To analyze the diffusion and perfusion parameters of central gland (CG) prostate cancer, stromal hyperplasia (SH), and glandular hyperplasia (GH) and to determine the role of these parameters in the differentiation of CG cancer from benign CG hyperplasia., Materials and Methods: In this institutional review board-approved (with waiver of informed consent), HIPAA-compliant study, 38 foci of carcinoma, 38 SH nodules, and 38 GH nodules in the CG were analyzed in 49 patients (26 with CG carcinoma) who underwent preoperative endorectal magnetic resonance (MR) imaging and radical prostatectomy. All carcinomas and hyperplastic foci on MR images were localized on the basis of histopathologic correlation. The apparent diffusion coefficient (ADC), the contrast agent transfer rate between blood and tissue (K(trans)), and extravascular extracellular fractional volume values for all carcinoma, SH, and GH foci were calculated. The mean, standard deviation, 95% confidence interval (CI), and range of each parameter were calculated. Receiver operating characteristic (ROC) and multivariate logistic regression analyses were performed for differentiation of CG cancer from SH and GH foci., Results: The average ADCs (× 10(-3) mm(2)/sec) were 1.05 (95% CI: 0.97, 1.11), 1.27 (95% CI: 1.20, 1.33), and 1.73 (95% CI: 1.64, 1.83), respectively, in CG carcinoma, SH foci, and GH foci and differed significantly, yielding areas under the ROC curve (AUCs) of 0.99 and 0.78, respectively, for differentiation of carcinoma from GH and SH. Perfusion parameters were similar in CG carcinomas and SH foci, with K(trans) yielding the greatest AUCs (0.75 and 0.58, respectively). Adding K(trans) to ADC in ROC analysis to differentiate CG carcinoma from SH increased sensitivity from 38% to 57% at 90% specificity without noticeably increasing the AUC (0.79)., Conclusion: ADCs differ significantly between CG carcinoma, SH, and GH, and the use of them can improve the differentiation of CG cancer from SH and GH. Combining K(trans) with ADC can potentially improve the detection of CG cancer., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100021/-/DC1., (© RSNA, 2010)

Improvements in the reliable diagnosis of preinvasive ductal carcinoma in situ (DCIS) by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are needed. In this study, we present a new characterization of early contrast kinetics of DCIS using high temporal resolution (HiT) DCE-MRI and compare it with other breast lesions and normal parenchyma. Forty patients with mammographic calcifications suspicious for DCIS were selected for HiT imaging using T(1)-weighted DCE-MRI with ∼7 s temporal resolution for 90 s post-contrast injection. Pixel-based and whole-lesion kinetic curves were fit to an empirical mathematical model (EMM) and several secondary kinetic parameters derived. Using the EMM parameterized and fitted concentration time curve for subsequent analysis allowed for calculation of kinetic parameters that were less susceptible to fluctuations due to noise. The parameters' initial area under the curve (iAUC) and contrast concentration at 1 min (C(1 min)) provided the highest diagnostic accuracy in the task of distinguishing pathologically proven DCIS from normal tissue. There was a trend for DCIS lesions with solid architectural pattern to exhibit a negative slope at 1 min (i.e. increased washout rate) compared to those with a cribriform pattern (p < 0.04). This pilot study demonstrates the feasibility of quantitative analysis of early contrast kinetics at high temporal resolution and points to the potential for such an analysis to improve the characterization of DCIS.

Pharmacokinetic modeling is a promising quantitative analysis technique for cancer diagnosis. However, diagnostic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the breast is commonly performed with low temporal resolution. This limits its clinical utility. We investigated for a range of temporal resolutions whether pharmacokinetic parameter estimation is impacted by the use of data-derived arterial input functions (AIFs), obtained via analysis of dynamic data from a reference tissue, as opposed to the use of a standard AIF, often obtained from the literature. We hypothesized that the first method allows the use of data at lower temporal resolutions than the second method. Test data were obtained by downsampling high-temporal-resolution rodent data via a k-space-based strategy. To fit the basic Tofts model, either the data-derived or the standard AIF was used. The resulting estimates of K(trans) and v(e) were compared with the standard estimates obtained by using the original data. The deviations in K(trans) and v(e), introduced when lowering temporal resolution, were more modest using data-derived AIFs compared with using a standard AIF. Specifically, lowering the resolution from 5 to 60 s, the respective changes in K(trans) were 2% (non-significant) and 18% (significant). Extracting the AIF from a reference tissue enables accurate pharmacokinetic parameter estimation for low-temporal-resolution data.

Rationale and Objectives: To quantify the relationship between dose of contrast administered and contrast kinetics of malignant breast lesions., Materials and Methods: A total of 108 patients with 120 malignant lesions were selected for an institutional review board-approved review. Dynamic magnetic resonance protocol: one pre- and three or five post-contrast (at a fixed volume of 20 mL of 0.5 M gadodiamide) images. Patients were stratified into groups based on dose of contrast administered, after calculation of body weight (kg): Dose Group 1, <0.122 mmol/kg; Dose Group 2, 0.123-0.155 mmol/kg; Dose Group, 3 > 0.155 mmol/kg. Analysis of kinetic curve shape was made according to the Breast Imaging Reporting and Data System lexicon. Several quantitative parameters were calculated including initial and peak enhancement percentage (E(1) and E(peak)). Linear regression was used to model the variation of kinetic parameters with dose., Results: There was no difference found in the qualitative Breast Imaging Reporting and Data System descriptors of curve shape between the three dose groups. There was a trend for E(1) and E(peak) to increase from Dose Group 1 to Dose Group 3 in malignant lesions overall, as well as in invasive ductal carcinoma lesions separately. Each decrement/increment of 0.05 mmol/kg in dose yielded a decrease/increase of 78% and 97% in E(1) for in situ and invasive cancers, respectively., Conclusion: Contrast should be administered at fixed dose to achieve comparable levels of lesion uptake in women of different weights. Our results suggest that reducing the contrast administered to 0.05 mmol/kg, as has been suggested for patients at risk of developing nephrogenic systemic fibrosis, could substantially decrease the observed initial enhancement in some cancers.

The c-Met receptor tyrosine kinase is emerging as a novel target in many solid tumors, including lung cancer. PHA-665752 was identified as a small molecule, ATP competitive inhibitor of the catalytic activity of the c-Met kinase. Here, we show that treatment with PHA665752 reduced NCI-H69 (small cell lung cancer) and NCI-H441 (non-small cell lung cancer) tumorigenicity in mouse xenografts by 99% and 75%, respectively. Reduction in tumor size was also observed by magnetic resonance imaging of tumors in mice. PHA665752 inhibited c-Met phosphorylation at the autophosphorylation and c-Cbl binding sites in mouse xenografts derived from non-small cell lung cancer cell lines (NCI-H441 and A549) and small cell lung cancer cell line (NCI-H69). PHA665752 also inhibited angiogenesis by >85% in all the abovementioned cell lines and caused an angiogenic switch which resulted in a decreased production of vascular endothelial growth factor and an increase in the production of the angiogenesis inhibitor thrombospondin-1. These studies show the feasibility of selectively targeting c-Met with ATP competitive small molecule inhibitors and suggest that PHA665752 may provide a novel therapeutic approach to lung cancer.

A pure electroporation injury leads to cell membrane disruption and subsequent osmotic swelling of the tissue. The state of water in the injured area of a tissue is changed and differs from a healthy tissue. Magnetic resonance imaging (MRI), which is very sensitive to the quality of the interaction between mobile (water) protons and a restricted (protein) proton pool, is therefore a useful tool to characterize this injury. Here, we present a protocol designed to measure the difference between the values of the transverse magnetic relaxation time (T2) in MRIs of healthy and electrically injured tissue. In addition, we present a method to evaluate the two main contributions to the MRI contrast, the degree of structural alteration of the cellular components (including a major contribution from membrane pores), and edema. The approach is useful in assessing the level of damage that electric shocks produce in muscle tissues, in that edema will resolve in time whereas structural changes require active repair mechanisms.

Purpose: To evaluate variability of a simplified method for measuring semiquantitative DCE-MRI parameters in patients with cancer and to explore effects of treatment with a putative anti-angiogenic compound., Materials and Methods: A total of 19 patients enrolled on treatment trials with the putative anti-angiogenic agent SU5416 underwent contrast enhanced examinations, and 11 had a second examination eight weeks post therapy. Contrast media concentration as a function of time was calculated using changes in signal and literature baseline T(1) values in normal muscle or liver reference tissue. Semiquantitative DCE-MRI parameters, including the area under the contrast concentration vs. time curve (AUC), were calculated for regions-of-interest in normal liver and muscle, and in tumors., Results: The coefficients of variation for pretherapy parameters in normal tissue were 11% to 37%. No significant changes were detected in normal liver over two months of therapy. In tumors and muscle, a significant decrease in the AUC and maximum contrast concentration was observed., Conclusion: Variability of semiquantitative DCE-MRI parameters utilizing a method based on known T(1) values in a reference tissue is low enough to detect changes in tumors during therapy. Use of this method as a pharmacodynamic marker should be further investigated., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: Vascular endothelial growth factor (VEGF) expression is prognostic in melanoma, and the activity of VEGF is mediated in part through the receptor tyrosine kinase Flk-1. A Phase II study of SU5416, a preferential inhibitor of Flk-1, was carried out in patients with metastatic melanoma to determine clinical response, tolerability, and changes in tumor vascular perfusion., Experimental Design: Patients with documented progressive disease and

Low frequency electrical currents traversing the body during electrical shock can produce tissue damage by effects of electrical forces on cellular organelles and proteins as well as by Joule heating beyond thermotolerance. Treatment for these different injuries are quite distinct. Therefore, it is important to accurately diagnose the form of injury. Here we discuss the use of MRI for this purpose.

Purpose: To acquire high spectral and spatial resolution (HiSS) MR images of the water resonance in rat brain, evaluate the lineshape of the water resonance in small voxels, and compare images derived from HiSS data with conventional images., Materials and Methods: Spectroscopic images of rat brain were obtained at 4.7 Tesla using phase encoding gradients only. Spectral resolution in each voxel was approximately 8 Hz and bandwidth was 1,000 Hz. Spatial resolution was approximately 250 microns in 1-mm slices. Images were synthesized to show the water signal integral, peak height, linewidth, resonance frequency, and asymmetry., Results: Two or more resolved components of the water resonance were detected in approximately 14% +/- 6% of voxels in the brains of eight rats. The water resonances in approximately 20% +/- 10% of voxels (n = 8) were highly asymmetric. Images with intensity proportional to water signal peak height, T(2)*, or to selected components of the water resonance showed features that were not evident in conventional images., Conclusions: The complexity of the water signal reflects the anatomy and physiology of the sub-voxelar environment, and may be a useful source of image contrast. HiSS imaging of brain provides accurate anatomic information, and may improve image contrast and delineation of subtle anatomic features., (Copyright 2002 Wiley-Liss, Inc.)

MR images can be acquired with high spectral and spatial resolution to precisely measure lineshapes of the water and fat resonances in each image voxel. Previous work suggests that the high-resolution spectral information can be used to improve image contrast, SNR, sensitivity to contrast agents and to physiologic and biochemical processes that affect local magnetic susceptibility gradients. The potential advantages of high-resolution spectroscopic imaging (SI) suggest that it might be useful for early detection and characterization of tumors. The present experiments evaluate the use of high-resolution SI to discriminate between metastatic and nonmetastatic rodent Dunning prostate tumors. SI datasets were obtained at 4.7 Tesla with an in-plane resolution of 350-500 micron in a single 1.0-mm slice, and 6-8 Hz spectral resolution, before and after i.v. injection of an iron oxide contrast agent. Images of water signal peak height in nonmetastatic tumors were smoother in the tumor interior than images of metastatic tumors (P <.004 by t-test) before contrast media injection. This difference was stronger in contrast-enhanced images (P <.0004). In addition, the boundary between the tumor and muscle was more clearly demarcated in nonmetastatic than metastatic tumors. Combinations of image texture, tumor edge morphology, and changes in T2* following contrast media injection improved discrimination between metastatic and nonmetastatic tumors. The data presented here do not demonstrate that effective discrimination between metastatic and nonmetastatic tumors depends on the use of high-resolution SI. However, the results suggest that SI and/or other MR methods that provide similar contrast might be used clinically for early and accurate detection of metastatic disease., (Copyright 2001 Wiley-Liss, Inc.)

Conventional MRI implicitly treats the proton signal as a single, narrow Lorentzian. However, water signals in vivo are often in homogeneously broadened and have multiple resolvable components. These components represent discrete populations of water molecules within each pixel which are affected differently by physiology and contrast agents. Accurate measurement of each component of the water resonance can improve anatomic and functional MR images and provide insight into the structure and dynamics of subpixelar microenvironments. This report describes high spectral and spatial resolution (HiSS) MR imaging of rodent prostate tumors before and after injection of a superparamagnetic contrast agent. HiSS datasets were used to synthesize images in which intensity is proportional to peak height, peak frequency, and linewidth. These images showed anatomic features which were not clearly delineated in conventional T(2) and gradient echo images. HiSS images obtained after injection of the contrast agent showed T *(2) and T(1) changes which were not seen in conventional images. These changes are associated with microvessel density and permeability. The results suggest HiSS with superparamagnetic contrast agents has the potential to improve characterization of tumors., (Copyright 2000 Wiley-Liss, Inc.)

The lack of information regarding the metabolism and pathophysiology of individual tumors limits, in part, both the development of new anti-cancer therapies and the optimal implementation of currently available treatments. Magnetic resonance [MR, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electron paramagnetic resonance (EPR)] provides a powerful tool to assess many aspects of tumor metabolism and pathophysiology. Moreover, since this information can be obtained nondestructively, pre-clinical results from cellular or animal models are often easily translated into the clinic. This review presents selected examples of how MR has been used to identify metabolic changes associated with apoptosis, detect therapeutic response prior to a change in tumor volume, optimize the combination of metabolic inhibitors with chemotherapy and/or radiation, characterize and exploit the influence of tumor pH on the effectiveness of chemotherapy, characterize tumor reoxygenation and the effects of modifiers of tumor oxygenation in individual tumors, image transgene expression and assess the efficacy of gene therapy. These examples provide an overview of several of the areas in which cellular and animal model studies using MR have contributed to our understanding of the effects of treatment on tumor metabolism and pathophysiology and the importance of tumor metabolism and pathophysiology as determinants of therapeutic response.

Rationale and Objectives: The authors evaluated whether fast spectroscopic imaging of water and fat resonances can produce high-quality anatomic magnetic resonance (MR) images of rodent tumors and human breast., Materials and Methods: Fast MR spectroscopic images of eight rats with mammary tumors were acquired by using a 4.7-T MR unit equipped with self-shielded gradient coils. MR spectroscopic images of four human breasts were acquired with a 1.5-T MR unit., Results: Artifacts due to eddy currents were minimal. Images synthesized from MR spectroscopic data, in which intensity was proportional to water signal peak height, were similar to T2-weighted MR images. Boundaries of rodent mammary tumors are similar but not identical on peak height-weighted and T2-weighted images. MR spectroscopic images of human breast showed improved detail compared to gradient-echo MR images., Conclusion: Preliminary results suggest that incorporation of fast MR spectroscopic imaging methods into many standard clinical MR imaging procedures may substantially improve image quality.

Tissue uptake of a fully extractable MR detectable tracer, deuterated water (D2O), was compared with that of a less extractable contrast agent, Gadolinium-DTPA-dimeglumine (Gd-DTPA), in rodent tumor and muscle tissue. This dual tracer method allowed calculation of relative (to muscle) tissue perfusion and extraction fraction of Gd-DTPA in each image pixel in vivo. Solutions of Gd-DTPA and D2O were injected intravenously into Fisher female rats (n = 9) with R3230 mammary adenocarcinomas implanted in the hind limb. Perfusion rate was approximately two times greater (P < 0.005 by paired t test) in tumor than in muscle. Gd-DTPA extraction fraction at the interface between tumor and muscle was 2.0 times the extraction fraction in normal muscle (P < 0.005 by paired t test). Extraction fraction at the tumor center was 1.6 times the extraction fraction in muscle (P < 0.01 by paired t test). High extraction fraction of Gd-DTPA correlated with high capillary permeability determined from Evans Blue staining. Low molecular weight Gd-DTPA derivatives are widely used in clinical practice, and their extraction fractions are crucial determinants of image contrast during the first few passes of the contrast agent bolus. Therefore spatially resolved measurements of contrast agent extraction fractions obtained in vivo have significant clinical utility. The data demonstrate that extraction of low molecular weight tracers is sensitive to increased permeability in tumor vasculature and that this increased permeability can be imaged.

A variety of treatments that modulate tumor oxygen tension are used clinically to improve the outcome of radiotherapy. High resolution, noninvasive measurements of the effects of these treatments would greatly facilitate the development of improved therapies and could guide treatment of cancer patients. Previous work demonstrated that magnetic resonance (MR) gradient echo imaging of the water proton resonance detects changes in T2* and T1 in tumors during hyperoxia that may reflect increased tumor oxygenation. This report describes the use of high resolution MR spectroscopic imaging with short repetition time (TR = 0.2 s) to improve the accuracy with which changes in T2* and T1 are measured. Mammary adenocarcinomas grown in the hind limbs of rats were studied. Carbogen inhalation was used to induce hyperoxia. A single 2-mm slice through the center of tumors and underlying muscle was imaged at 4.7 Tesla with in-plane resolution of approximately 1.2 mm and frequency resolution of 5.8 Hz. The peak integral increased by an average of 6% in tumors during carbogen inhalation suggesting a decrease in T1 (n = 8, P < 0.001). Peak height increased by an average of 15% in tumors during carbogen inhalation (n = 8, P < 0.001). The large difference between increases in peak height and peak integral demonstrates that the width of the water resonance decreased. Assuming a Lorentzian lineshape, an average increase of 12% in T2* was observed in tumors. In muscle, peak integral and peak height increased slightly (about 1.2% and 3%, respectively; P < 0.02) during carbogen inhalation but no significant change in T2* was observed. Spectroscopic imaging detects changes in the water proton resonance in tumors during hyperoxia accurately and reproducibly with high signal-to-noise ratio and allows clear separation of T1 and T2* effects. Increases in T2* may be due to decreased deoxyhemoglobin in tumor blood vessels (i.e., the BOLD effect) and may provide a clinically useful index of increases in tumor oxygenation.

We have used very low-frequency electron paramagnetic resonance (EPR) oximetry to measure the change in oxygen concentration (delta pO2) due to change in breathing atmosphere in FSa and NFSa fibrosarcomas implanted in the legs of C3H mice infused with perfluoro-octylbromine (PFOB). Measurements in each tumor were made before and after the administration of the high-density (47% v/v) perfluorocarbon PFOB, perflubron (Alliance Pharmaceutical Corporation, San Diego, CA). Measurements in each tumor were also made, after the administration of the PFOB, both before (PFOB/air) and after the administration of carbogen (95% O2 + 5% CO2, PFOB/carbogen). Large changes (delta p02) relative to PFOB/air oxygenation were seen with the administration of PFOB/carbogen. No significant difference in oxygen concentration was seen between air-breathing mice with and without PFOB. The mean delta pO2 for FSa tumors was 13 +/- 6 torr, while the mean for NFSa fibrosarcomas was 28 +/- 7 torr. There were such large intertumor differences that the trend toward a smaller change in the more hypoxic FSa tumors was not significant (P = 0.13). This paper describes a novel method of measuring differences in oxygenation in tumor tissues. The results of such measurements indicate large differences in pO2 response to different breathing atmospheres in PFOB-infused tumors of similar histology. The intertumor delta pO2 differences may correlate with differences in radiation response.

Vibrations in a granular material can spontaneously produce convection rolls reminiscent of those seen in fluids. Magnetic resonance imaging provides a sensitive and noninvasive probe for the detection of these convection currents, which have otherwise been difficult to observe. A magnetic resonance imaging study of convection in a column of poppy seeds yielded data about the detailed shape of the convection rolls and the depth dependence of the convection velocity. The velocity was found to decrease exponentially with depth; a simple model for this behavior is presented here.

Experiments were performed to determine whether changes in T2*-weighted MR images during and after hyperoxia differentiate tumors from normal tissue. Mammary adenocarcinomas implanted in the right hind limbs of rats were studied. Gradient echo images were obtained at 2 Tesla with an evolution time of 20 ms and a recycle time of 1 s. Breathing gas was either air or 100% O2. Significant increases in image intensity were observed in tumor centers and rims during hyperoxia while much smaller changes were detected in the surrounding muscle. The relaxation rate (1/T2*) in tumors decreased during hyperoxia by an average of 2.5 +/- 1.0 s-1, while in muscle the average change was an increase of 0.6 +/- 2.1 s-1. The largest decreases in relaxation rate were detected in non-necrotic tumor regions with relatively low density of blood vessels. Immediately following hyperoxia significant decreases in intensity were detected in tumors while much smaller decreases were detected in the surrounding muscle.

Rationale and Objectives: Hepatic embolization combined with intra-arterial administration of cytostatic drugs (chemoembolization) is frequently used to treat primary and metastatic cancers to the liver. Quantitative phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to assess the metabolic state of hepatic cancers and their metabolic response to chemoembolization., Methods: Fifteen localized 31P MRS studies were performed on five patients with liver tumors. Thirteen healthy volunteers served as controls. Metabolite ratios and molar metabolite concentrations were calculated., Results: Untreated hepatic tumors, relative to normal controls, showed elevated phosphomonoester/adenosine triphosphate (PME/ATP) ratios, reduced concentrations of ATP and inorganic phosphate (Pi), and normal phosphodiester (PDE) concentrations. As an acute response to chemoembolization, ATP, PME, and/or PDE concentrations diminished, whereas Pi concentrations increased or stayed relatively constant. Long-term follow-up after chemoembolization showed decreased PME/ATP and increased ATP concentrations in the absence of changes on standard magnetic resonance and computed tomographic images., Conclusions: These preliminary spectroscopic data suggest that quantitative 31P MRS can be successfully used to monitor directly metabolic response to hepatic chemoembolization.

The purpose of this study was to investigate whether substrate deprivation acutely and selectively decreases ATP concentration in an experimental sarcoma. Two methods of substrate deprivation were examined: glycolysis was inhibited using 2-deoxyglucose (2DG), and plasma substrate levels were reduced using insulin. The effects of treatment on tumor ATP, inorganic phosphate, and pH were studied by 31P nuclear magnetic resonance spectroscopy. 2DG (2 g/kg) was administered i.p. to rats bearing s.c. methylcholanthrene-induced sarcomas. Inhibition of glycolysis by 2DG caused a 52 +/- 13% (SE) decrease in the tumor ATP to inorganic phosphate ratio, associated with a decrease in pH of 0.38 +/- 0.10 unit. The same dose of 2DG caused no significant change in the ratio of phosphocreatine to ATP in brain. Insulin (125 units/kg, i.p.) caused a 68% decline in plasma glucose and a 71% decline in betahydroxybutyrate compared to saline-treated animals. Concomitantly, 31P nuclear magnetic resonance spectroscopy detected a 48 +/- 13% decrease in sarcoma ATP, with a reciprocal elevation of inorganic phosphate in insulin-treated animals. In contrast, the brain phosphocratine/ATP ratio was unaffected by insulin. These results suggest that large tumors are acutely sensitive to inhibition of glycolysis and reductions in plasma levels of substrates for oxidative phosphorylation and glycolysis, while the brain is unaffected. In addition, this work provides support for the use of 31P nuclear magnetic resonance spectroscopy to monitor tumor response to therapy.