Technical Note: A custom-designed flexible MR coil array for spine radiotherapy treatment planning.

PURPOSE: To assess the performance and optimize the MR image quality when using a custom-built flexible radiofrequency (RF) spine coil array fitted between the immobilization device and the patient for spine radiotherapy treatment planning. METHODS: A 32 channel flexible custom-designed receive-only coil array has been developed for spine radiotherapy simulation for a 3 T Philips MR scanner. Coil signal-to-noise performance and interactions with standard vendor hardware were assessed. In four volunteers, immobilization molds were created with a dummy version of the array within the mold, and subjects were scanned using the custom array in the mold. Phantoms and normal volunteers were scanned with both the custom spine coil array and the vendor's FDA-approved in-table posterior coil array to compare performance. RESULTS: The superior-inferior field of view for the custom spine array was ~30 cm encompassing at least 10 vertebrae. A noise correlation matrix showed at least 25 dB isolation between all coil elements. Signal-to-noise ratio (SNR) calculated on a phantom scan at the depth of the spinal cord was a factor of 3 higher with the form-fit spine array as compared to the vendor's posterior coil array. The body coil B1 transmit map was equivalent with and without the spine array in place demonstrating that the elements are decoupled from the body coil. Volunteer imaging showed improved SNR as compared to the vendor's posterior coil array. The custom array permitted a high degree of acceleration making possible the acquisition of isotropic high-resolution 1.1 × 1.1 × 1.1 mm3 three-dimensional data set over a 30-cm section of the spine in less than 5 min. CONCLUSION: The custom-designed form-fitting flexible spine coil array provided enhanced SNR and increased acceleration compared to the vendor's posterior array. Future studies will assess MR-based spinal cord imaging with the custom coil in comparison to CT myelogram.

Comparison of Motion-Insensitive T2-Weighted MRI Pulse Sequences for Visualization of the Prostatic Urethra During MR Simulation.

PURPOSE: The use of magnetic resonance imaging (MRI) for radiation therapy simulation is growing because of its ability to provide excellent delineation of target tissue and organs at risk. With the use of hypofractionated schemes in prostate cancer, urethral sparing is essential; however, visualization of the prostatic urethra can be challenging because of the presence of benign prostatic hyperplasia as well as respiratory motion artifacts. The goal of this study was to compare the utility of 2 motion-insensitive, T2-weighted MRI pulse sequences for urethra visualization in the setting of MRI-based simulation. METHODS AND MATERIALS: Twenty-two patients undergoing MRI simulation without Foley catheters were imaged on a 3 Tesla MRI scanner between October 2018 and January 2019. Sagittal multislice data were acquired using (1) MultiVane XD radial sampling with parallel imaging acceleration (MVXD) and (2) single-shot fast-spin-echo (SSFSE) sequences with acquisition times of 2 to 3 minutes per sequence. For each examination, 2 genitourinary radiologists scored prostatic urethra visibility on a 1-to-5 scale and rated the signal-to-noise ratio and the presence of artifacts in each series. RESULTS: Urethral visibility was scored higher in the MVXD series than in the SSFSE series in 18 of 22 cases (Reader 1) and 17 of 22 cases (Reader 2). The differences in scores between MVXD and SSFSE were statistically significant for both readers (P < .0001 for both, paired Student's t-test) and interobserver agreement was high (Cohen's kappa = 0.67). Both readers found the signal-to-noise ratio of the MVXD sequence to be superior in all cases. The MVXD sequence was found to generate more artifacts than the SSFSE sequence, but these tended to appear in the periphery and did not affect the ability to visualize the urethra. CONCLUSIONS: A radial T2-weighted multislice pulse sequence was superior to an SSFSE sequence for visualization of the urethra in the setting of magnetic resonance simulation for prostate cancer.

Limited accuracy of DCE-MRI in identification of pathological complete responders after chemoradiotherapy treatment for rectal cancer.

OBJECTIVES: To examine whether post-chemoradiotherapy (CRT) DCE-MRI can identify rectal cancer patients with pathologic complete response (pCR). METHODS: From a rectal cancer surgery database 2007-2014, 61 consecutive patients that met the following inclusion criteria were selected for analysis: (1) stage II/III primary rectal adenocarcinoma; (2) received CRT; (3) underwent surgery (4); underwent rectal DCE-MRI on a 1.5-T MRI scanner. Two experienced radiologists, in consensus, drew regions of interest (ROI) on the sagittal DCE-MRI image in the tumour bed. These were exported from ImageJ to in-house Matlab code for modelling using the Tofts model. K trans, K ep and v e values were compared to pathological response. RESULTS: Of the 61 initial patients, 37 had data considered adequate for fitting to obtain perfusion parameters. Among the 13 men and 24 women, median age 53 years, there were 8 pCR (22 %). K trans could not distinguish patients with pCR. For patients with 90 % or greater response, mean K trans and K ep values were statistically significant (p = 0.032 and 0.027, respectively). Using a cutoff value of K trans = 0.25 min-1, the AUC was 0.71. CONCLUSION: K trans could be used to identify patients with 90 % or more response to chemoradiotherapy for rectal cancer with an AUC of 0.7. KEY POINTS: • Chemoradiotherapy for rectal cancer causes decreased blood flow and permeability in the tumour bed. • Lower values of blood flow and permeability correlate with good tumour response. • K trans of 0.25min -1 best identifies patients with ≥90 % response with AUC 0.71.

Long-term outcome of magnetic resonance spectroscopic image-directed dose escalation for prostate brachytherapy.

PURPOSE: To report the long-term control and toxicity outcomes of patients with clinically localized prostate cancer, who underwent low-dose-rate prostate brachytherapy with magnetic resonance spectroscopic image (MRSI)-directed dose escalation to intraprostatic regions. METHODS AND MATERIALS: Forty-seven consecutive patients between May 2000 and December 2003 were analyzed retrospectively. Each patient underwent a preprocedural MRSI, and MRS-positive voxels suspicious for malignancy were identified. Intraoperative planning was used to determine the optimal seed distribution to deliver a standard prescription dose to the entire prostate, while escalating the dose to MRS-positive voxels to 150% of prescription. Each patient underwent transperineal implantation of radioactive seeds followed by same-day CT for postimplant dosimetry. RESULTS: The median prostate D90 (minimum dose received by 90% of the prostate) was 125.7% (interquartile range [IQR], 110.3-136.5%) of prescription. The median value for the MRS-positive mean dose was 229.9% (IQR, 200.0-251.9%). Median urethra D30 and rectal D30 values were 142.2% (137.5-168.2%) and 56.1% (40.1-63.4%), respectively. Median followup was 86.4 months (IQR, 49.8-117.6). The 10-year actuarial prostate-specific antigen relapse-free survival was 98% (95% confidence interval, 93-100%). Five patients (11%) experienced late Grade 3 urinary toxicity (e.g., urethral stricture), which improved after operative intervention. Four of these patients had dose-escalated voxels less than 1.0 cm from the urethra. CONCLUSIONS: Low-dose-rate brachytherapy with MRSI-directed dose escalation to suspicious intraprostatic regions exhibits excellent long-term biochemical control. Patients with dose-escalated voxels close to the urethra were at higher risk of late urinary stricture.

Prostate MRSI predicts outcome in radical prostatectomy patients.

BACKGROUND: New non-invasive methods are needed for sub-stratifying high-risk prostate cancer patients. Magnetic resonance spectroscopic imaging (MRSI) maps metabolites in prostate cancer, providing information on tumor aggressiveness and volume. PURPOSE: To investigate the correlation between MRSI and treatment failure (TF) after radical prostatectomy (RP). METHODS: Two-hundred sixty-two patients who underwent endorectal MRI/MRSI followed by RP at our institution from 2003 to 2007 were studied. MRI stage, number of voxels in the MRSI index lesion (NILV), number of high-grade voxels (NHGV), and number of voxels containing undetectable polyamines (NUPV) were derived. Clinical outcome was followed until August, 2014. Treatment failure was defined as 1) biochemical recurrence (BCR), 2) persistently detectable PSA after RP, or 3) adjuvant therapy initiated in the absence of BCR. MRI/MRSI features and clinical parameters were compared to TF by univariate Cox Proportional Hazards Regression. After backward selection, each MRSI parameter was included in a separate regression model adjusted for NCCN-based clinical risk score (CRS), number of biopsy cores positive (NPC), and MRI stage. RESULTS: In univariate analysis, all clinical variables were associated with TF in addition to MRI stage, NILV, NHGV, and NUPV. In multivariate analysis, NILV, NHGV, and NUPV were also significant risk factors for TF (p=0.016, p=0.002, p=0.006, respectively). The association between the number of tumor voxels with undetectable polyamines and the probability of treatment failure has not been previously reported. The number of MRSI cancer voxels correlated with extracapsular extension (ECE) (p<0.0001). CONCLUSIONS: MRSI was associated with post-radical prostatectomy treatment failure in models adjusted for the number of positive biopsy cores and clinical risk score. This is the first report that in radical prostatectomy patients MRSI has an association with treatment failure independent of the number of positive biopsy cores. MRSI may help the clinician determine whether patients with high risk disease who undergo RP are candidates for specialized additional treatment.

Anatomic segmentation improves prostate cancer detection with artificial neural networks analysis of 1H magnetic resonance spectroscopic imaging.

PURPOSE: To assess whether an artificial neural network (ANN) model is a useful tool for automatic detection of cancerous voxels in the prostate from (1)H-MRSI datasets and whether the addition of information about anatomical segmentation improves the detection of cancer. MATERIALS AND METHODS: The Institutional Review Board approved this HIPAA-compliant study and waived informed consent. Eighteen men with prostate cancer (median age, 55 years; range, 36-71 years) who underwent endorectal MRI/MRSI before radical prostatectomy were included in this study. These patients had at least one cancer area on whole-mount histopathological map and at least one matching MRSI voxel suspicious for cancer detected. Two ANN models for automatic classification of MRSI voxels in the prostate were implemented and compared: model 1, which used only spectra as input, and model 2, which used the spectra plus information from anatomical segmentation. The models were trained, tested and validated using spectra from voxels that the spectroscopist had designated as cancer and that were verified on histopathological maps. RESULTS: At ROC analysis, model 2 (AUC = 0.968) provided significantly better (P = 0.03) classification of cancerous voxels than did model 1 (AUC = 0.949). CONCLUSION: Automatic analysis of prostate MRSI to detect cancer using ANN model is feasible. Application of anatomical segmentation from MRI as an additional input to ANN improves the accuracy of detecting cancerous voxels from MRSI.

Relationships between LDH-A, lactate, and metastases in 4T1 breast tumors.

PURPOSE: To investigate the relationship between lactate dehydrogenase A (LDH-A) expression, lactate concentration, cell metabolism, and metastases in murine 4T1 breast tumors. EXPERIMENTAL DESIGN: Inhibition of LDH-A expression and protein levels were achieved in a metastatic breast cancer cell line (4T1) using short hairpin RNA (shRNA) technology. The relationship between tumor LDH-A protein levels and lactate concentration (measured by magnetic resonance spectroscopic imaging, MRSI) and metastases was assessed. RESULTS: LDH-A knockdown cells (KD9) showed a significant reduction in LDH-A protein and LDH activity, less acid production, decreased transwell migration and invasion, lower proliferation, reduced glucose consumption and glycolysis, and increase in oxygen consumption, reactive oxygen species (ROS), and cellular ATP levels, compared with control (NC) cells cultured in 25 mmol/L glucose. In vivo studies showed lower lactate levels in KD9, KD5, and KD317 tumors than in NC or 4T1 wild-type tumors (P < 0.01), and a linear relationship between tumor LDH-A protein expression and lactate concentration. Metastases were delayed and primary tumor growth rate decreased. CONCLUSIONS: We show for the first time that LDH-A knockdown inhibited the formation of metastases, and was accompanied by in vivo changes in tumor cell metabolism. Lactate MRSI can be used as a surrogate to monitor targeted inhibition of LDH-A in a preclinical setting and provides a noninvasive imaging strategy to monitor LDH-A-targeted therapy. This imaging strategy can be translated to the clinic to identify and monitor patients who are at high risk of developing metastatic disease.

Serial measurement of hepatic lipids during chemotherapy in patients with colorectal cancer: a 1 H MRS study.

Hepatic steatosis is a hallmark of chemotherapy-induced liver injury. We made serial (1) H MRS measurements of hepatic lipids in patients over the time course of a 24-week chemotherapeutic regimen to determine whether (1) H MRS could be used to monitor the progression of chemotherapy-induced steatosis. Thirty-four patients with stage III or IV colorectal cancer receiving 5-fluorouracil, folinic acid and oxaliplatin (n=21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n=13) were studied prospectively. (1) H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A (1) H MR spectrum was acquired from the liver during a breath hold and the ratio of fat to fat+water (FFW) was calculated to give a measure of hepatic triglycerides (HTGCs). The methodology was histologically validated in 18 patients and the reproducibility was assessed in 16 normal volunteers. Twenty-seven patients completed baseline, 6-week and 24-week (1) H MRS examinations and one was censored. Thirteen of 26 patients (50%) showed an increase in FFW after completion of treatment. Six patients (23%) developed hepatic steatosis and two patients converted from steatosis to nonsteatotic liver. Patients whose 6-week hepatic lipid levels had increased significantly relative to baseline also had a high probability of lipid elevation relative to baseline at the completion of treatment. Serial (1) H MRS is effective for the monitoring of HTGC changes during chemotherapy and for the detection of chemotherapy-associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks.

Performance characteristics of MR imaging in the evaluation of clinically low-risk prostate cancer: a prospective study.

PURPOSE: To prospectively evaluate diagnostic performance of T2-weighted magnetic resonance (MR) imaging and MR spectroscopic imaging in detecting lesions stratified by pathologic volume and Gleason score in men with clinically determined low-risk prostate cancer. MATERIALS AND METHODS: The institutional review board approved this prospective, HIPAA-compliant study. Written informed consent was obtained from 183 men with clinically low-risk prostate cancer (cT1-cT2a, Gleason score≤6 at biopsy, prostate-specific antigen [PSA] level<10 ng/mL [10 µg/L]) undergoing MR imaging before prostatectomy. By using a scale of 1-5 (score 1, definitely no tumor; score 5, definitely tumor), two radiologists independently scored likelihood of tumor per sextant on T2-weighted images. Two spectroscopists jointly recorded locations of lesions with metabolic features consistent with tumor on MR spectroscopic images. Whole-mount step-section histopathologic analysis constituted the reference standard. Diagnostic performance at sextant level (T2-weighted imaging) and detection sensitivities (T2-weighted imaging and MR spectroscopic imaging) for lesions of 0.5 cm3 or larger were calculated. RESULTS: For T2-weighted imaging, areas under the receiver operating characteristic curves for sextant-level detection were 0.77 (reader 1) and 0.82 (reader 2). For lesions of ≥0.5 cm3 and, 1

Preoperative nomograms incorporating magnetic resonance imaging and spectroscopy for prediction of insignificant prostate cancer.

UNLABELLED: Study Type--Prognosis (case series). Level of Evidence 4. What's known on the subject? And what does the study add? Nomograms are available that combine clinical and biopsy findings to predict the probability of pathologically insignificant prostate cancer in patients with clinically low-risk disease. Based on data from patients with Gleason score 6, clinical stage ≤ T2a and PSA <20 ng/ml, our group developed the first nomogram models for predicting insignificant prostate cancer that incorporated clinical data, detailed biopsy data and findings from MRI or MRI/MRSI (BJU Int. 2007;99(4):786-93). When tested retrospectively, these MR models performed significantly better than standard clinical models with and without detailed biopsy data. We prospectively validated the previously published MR-based nomogram models in a population of patients with Gleason score 6, clinical stage ≤ T2a and PSA <10 ng/ml. Based on data from this same population, we also developed two new models for predicting insignificant prostate cancer that combine MR findings and clinical data without detailed biopsy data. Upon initial testing, the new MR models performed significantly better than a clinical model lacking detailed biopsy data. OBJECTIVES: • To validate previously published nomograms for predicting insignificant prostate cancer (PCa) that incorporate clinical data, percentage of biopsy cores positive (%BC+) and magnetic resonance imaging (MRI) or MRI/MR spectroscopic imaging (MRSI) results. • We also designed new nomogram models incorporating magnetic resonance results and clinical data without detailed biopsy data. Nomograms for predicting insignificant PCa can help physicians counsel patients with clinically low-risk disease who are choosing between active surveillance and definitive therapy. PATIENTS AND METHODS: • In total, 181 low-risk PCa patients (clinical stage T1c-T2a, prostate-specific antigen level <10 ng/mL, biopsy Gleason score of 6) had MRI/MRSI before surgery. • For MRI and MRI/MRSI, the probability of insignificant PCa was recorded prospectively and independently by two radiologists on a scale from 0 (definitely insignificant) to 3 (definitely significant PCa). • Insignificant PCa was defined on surgical pathology. • There were four models incorporating MRI or MRI/MRSI and clinical data with and without %BC+ that were compared with a base clinical model without %BC and a more comprehensive clinical model with %BC+. Prediction accuracy was assessed using areas under receiver-operator characteristic curves. RESULTS: • At pathology, 27% of patients had insignificant PCa, and the Gleason score was upgraded in 56.4% of patients. • For both readers, all magnetic resonance models performed significantly better than the base clinical model (P ≤ 0.05 for all) and similarly to the more comprehensive clinical model. CONCLUSIONS: • Existing models incorporating magnetic resonance data, clinical data and %BC+ for predicting the probability of insignificant PCa were validated. • All MR-inclusive models performed significantly better than the base clinical model.

Preclinical study of treatment response in HCT-116 cells and xenografts with (1) H-decoupled (31) P MRS.

The topoisomerase I inhibitor, irinotecan, and its active metabolite SN-38 have been shown to induce G(2) /M cell cycle arrest without significant cell death in human colon carcinoma cells (HCT-116). Subsequent treatment of these G(2) /M-arrested cells with the cyclin-dependent kinase inhibitor, flavopiridol, induced these cells to undergo apoptosis. The goal of this study was to develop a noninvasive metabolic biomarker for early tumor response and target inhibition of irinotecan followed by flavopiridol treatment in a longitudinal study. A total of eleven mice bearing HCT-116 xenografts were separated into two cohorts where one cohort was administered saline and the other treated with a sequential course of irinotecan followed by flavopiridol. Each mouse xenograft was longitudinally monitored with proton ((1) H)-decoupled phosphorus ((31) P) magnetic resonance spectroscopy (MRS) before and after treatment. A statistically significant decrease in phosphocholine (p = 0.0004) and inorganic phosphate (p = 0.0103) levels were observed in HCT-116 xenografts following treatment, which were evidenced within twenty-four hours of treatment completion. Also, a significant growth delay was found in treated xenografts. To discern the underlying mechanism for the treatment response of the xenografts, in vitro HCT-116 cell cultures were investigated with enzymatic assays, cell cycle analysis, and apoptotic assays. Flavopiridol had a direct effect on choline kinase as measured by a 67% reduction in the phosphorylation of choline to phosphocholine. Cells treated with SN-38 alone underwent 83 ± 5% G(2) /M cell cycle arrest compared to untreated cells. In cells, flavopiridol alone induced 5 ± 1% apoptosis while the sequential treatment (SN-38 then flavopiridol) resulted in 39 ± 10% apoptosis. In vivo (1) H-decoupled (31) P MRS indirectly measures choline kinase activity. The decrease in phosphocholine may be a potential indicator of early tumor response to the sequential treatment of irinotecan followed by flavopiridol in noninvasive and/or longitudinal studies.

31P MR spectroscopic imaging detects regenerative changes in human liver stimulated by portal vein embolization.

PURPOSE: First, to evaluate hepatocyte phospholipid metabolism and energetics during liver regeneration stimulated by portal vein embolization (PVE) using proton-decoupled (31)P MR spectroscopic imaging ((31)P-MRSI). Second, to compare the biophysiologic differences between hepatic regeneration stimulated by PVE and by partial hepatectomy (PH). MATERIALS AND METHODS: Subjects included six patients with hepatic metastases from colorectal cancer who were scheduled to undergo right PVE before definitive resection of right-sided tumor. (31)P-MRSI was performed on the left liver lobe before PVE and 48 h following PVE. Normalized quantities of phosphorus-containing hepatic metabolites were analyzed from both visits. In addition, MRSI data at 48 h following partial hepatectomy were compared with the data from the PVE patients. RESULTS: At 48 h after PVE, the ratio of phosphomonoesters to phosphodiesters in the nonembolized lobe was significantly elevated. No significant changes were found in nucleoside triphosphates (NTP) and Pi values. The phosphomonoester (PME) to phosphodiester (PDE) ratio in regenerating liver 48 h after partial hepatectomy was significantly greater than PME/PDE 48 h after PVE. CONCLUSION: (31)P-MRSI is a valid technique to noninvasively evaluate cell membrane metabolism following PVE. The different degree of biochemical change between partial hepatectomy and PVE indicates that hepatic growth following these two procedures does not follow the same course.

An exploratory study of endorectal magnetic resonance imaging and spectroscopy of the prostate as preoperative predictive biomarkers of biochemical relapse after radical prostatectomy.

PURPOSE: Radical prostatectomy has significant side effects. Preoperative information predicting its long-term outcome would be valuable to patients and physicians. We determined whether pretreatment endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging predicts biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: Of 202 patients who underwent endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging from January 2000 to December 2002 before radical prostatectomy 130 satisfied study inclusion criteria and were included in analysis. We compared imaging factors with potential predictive capability to biochemical recurrence data, including magnetic resonance imaging risk score based on local disease extent and magnetic resonance spectroscopic imaging index lesion characteristics, such as the number of voxels and degree of metabolic abnormality (magnetic resonance spectroscopic imaging grade). We evaluated associations of these imaging variables with time to biochemical recurrence by Cox proportional hazards regression adjusted for known predictors of biochemical recurrence, such as stage, grade and prostate specific antigen. RESULTS: At a median 68-month followup there were 26 biochemical failures. Risk score, lesion volume and high grade voxels each correlated with time to biochemical recurrence. In a model combining clinical parameters risk score, lesion volume and at least 1 high grade voxel the magnetic resonance spectroscopic imaging variables remained significant but the magnetic resonance imaging score dropped out. CONCLUSIONS: Index lesion volume on magnetic resonance spectroscopic imaging and high grade magnetic resonance spectroscopic imaging voxels correlate with time to biochemical recurrence after radical prostatectomy even when adjusted for clinical data. Results suggest the preoperative predictive usefulness of endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging in patients considering radical prostatectomy.

Prostate tumor volume measurement with combined T2-weighted imaging and diffusion-weighted MR: correlation with pathologic tumor volume.

PURPOSE: To retrospectively determine the accuracy of diffusion-weighted (DW) magnetic resonance (MR) imaging for identifying cancer in the prostate peripheral zone (PZ) and to assess the accuracy of tumor volume measurements made with T2-weighted imaging and combined T2-weighted and DW MR imaging by using surgical pathologic examination as the reference standard. MATERIALS AND METHODS: The institutional review board issued a waiver of informed consent for this HIPAA-compliant study. Forty-two patients underwent endorectal MR at 1.5 T before undergoing radical prostatectomy for prostate cancer and had at least one PZ tumor larger than 0.1 cm(3) at surgical pathologic examination. On T2-weighted images, an experienced radiologist outlined suspected PZ tumors. Two apparent diffusion coefficient (ADC) cutoff values were identified by using the Youden index and published literature. Image cluster analysis was performed on voxels within the suspected tumor regions. Associations between volume measurements from imaging and from pathologic examination were assessed by using concordance correlation coefficients (CCCs). The sensitivity and specificity of ADCs for identifying malignant PZ voxels were calculated. RESULTS: In identifying malignant voxels, respective ADC cutoff values of 0.0014 and 0.0016 mm(2)/sec yielded sensitivity of 82% and 95% and specificity of 85% and 65%, respectively. Sixty PZ cancer lesions larger than 0.1 cm(3) were found at pathologic examination; 43 were detected by the radiologist. CCCs between imaging and pathologic tumor volume measurements were 0.36 for T2-weighted imaging, and 0.46 and 0.60 for combined T2-weighted and DW MR imaging with ADC cutoffs of 0.0014 and 0.0016 mm(2)/sec, respectively; the CCC of combined T2-weighted and DW MR imaging (ADC cutoff, 0.0016 mm(2)/sec) was significantly higher (P = .006) than that of T2-weighted imaging alone. CONCLUSION: Adding DW MR to T2-weighted imaging can significantly improve the accuracy of prostate PZ tumor volume measurement. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/252/2/449/DC1.

Prediction of prostate cancer recurrence using magnetic resonance imaging and molecular profiles.

PURPOSE: To evaluate whether pretreatment magnetic resonance imaging (MRI)/MR spectroscopic imaging (MRSI) findings and molecular markers in surgical specimens correlate with each other and with pretreatment clinical variables (biopsy Gleason score, clinical stage, and prostate-specific antigen level) and whether they contribute incremental value in predicting prostate cancer recurrence. EXPERIMENTAL DESIGN: Eighty-eight prostate cancer patients underwent MRI/MRSI before radical prostatectomy; imaging findings were scored on a scale of 1 to 7 (no tumor seen-lymph node metastasis). Ki-67, phospho-Akt, and androgen receptor expression in surgical specimens were assessed by immunohistochemistry. To examine correlations between markers and imaging scores, Spearman's correlation was used. To test whether markers and imaging scores differed by clinical stage or Gleason score, Wilcoxon's rank sum test was used. To examine time to recurrence, the methods of Kaplan-Meier were used. Cox proportional hazards models were built and their concordance indices (C-indices) were calculated to evaluate prediction of recurrence. RESULTS: All markers correlated moderately strongly with MRI/MRSI score (all correlation coefficients >0.5). Markers and MRI/MRSI score were strongly associated with clinical stage and biopsy Gleason score (P < 0.01 for all). At last follow-up, 27 patients had recurrence. C-indices for MRI/MRSI score and all markers were associated with time to recurrence and ranged from 0.78 to 0.89. A Cox model combining all clinical predictors had a C-index of 0.89; the C-index increased to 0.95 when MRI/MRSI score was added and to 0.97 when markers were also added. CONCLUSIONS: MRI/MRSI findings and molecular markers correlated well with each other and contributed incremental value to clinical variables in predicting prostate cancer recurrence.

Correlation of MR imaging and MR spectroscopic imaging findings with Ki-67, phospho-Akt, and androgen receptor expression in prostate cancer.

PURPOSE: To retrospectively assess whether magnetic resonance (MR) imaging and MR spectroscopic imaging and selected molecular markers correlate with each other and with clinically insignificant and significant prostate cancer (PCa), as defined at surgical pathologic analysis. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant study and waived informed consent. Eighty-nine men (mean age, 63 years; range, 46-79 years) with biopsy-proved PCa underwent combined endorectal MR imaging and MR spectroscopic imaging before radical prostatectomy. Suspicion of clinically insignificant PCa was retrospectively and separately recorded for MR imaging and combined MR imaging and MR spectroscopic imaging by using a scale of 0-3. Clinically insignificant PCa was pathologically defined as organ-confined cancer of 0.5 cm(3) or less without poorly differentiated elements. Prostatectomy specimens underwent immunohistochemical analysis for three molecular markers: Ki-67, phospho-Akt (pAkt), and androgen receptor (AR). To examine differences in marker levels for clinically insignificant and significant cancer, a Wilcoxon rank sum test was used. To examine correlations between marker levels and MR imaging or combined MR imaging and MR spectroscopic imaging scores, the Spearman correlation was used. RESULTS: Twenty-one (24%) patients had clinically insignificant and 68 (76%) had clinically significant PCa at surgical pathologic review. All markers were significantly correlated with MR imaging and combined MR imaging and MR spectroscopic imaging findings (all correlation coefficients >0.5). In differentiating clinically insignificant from clinically significant PCa, areas under the receiver operating characteristic curves for Ki-67, AR, pAkt, MR imaging, and combined MR imaging and MR spectroscopic imaging were 0.75, 0.78, 0.80, 0.85, and 0.91, respectively. CONCLUSION: The use of pretreatment MR imaging or combined MR imaging and MR spectroscopic imaging and molecular marker analyses of biopsy samples could facilitate better treatment selection. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/250/3/803/DC1.

Regarding the focal treatment of prostate cancer: inference of the Gleason grade from magnetic resonance spectroscopic imaging.

PURPOSE: To quantify, as a function of average magnetic resonance spectroscopy (MRS) score and tumor volume, the probability that a cancer-suspected lesion has an elevated Gleason grade. METHODS AND MATERIALS: The data consist of MRS imaging ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason grade, and lesion volume. The data were analyzed using a logistic model. RESULTS: For both low and high Gleason score biopsy lesions, the probability of pathologic Gleason score >/=4+3 increases with lesion volume. At low values of R a lesion volume of at least 15-20 voxels is needed to reach a probability of success of 80%; the biopsy result helps reduce the prediction uncertainty. At larger MRS ratios (R > 6) the biopsy result becomes essentially uninformative once the lesion volume is >12 voxels. With the exception of low values of R, for lesions with low Gleason score at biopsy, the MRS ratios serve primarily as a selection tool for assessing lesion volumes. CONCLUSIONS: In patients with biopsy Gleason score >/=4+3, high MRS imaging tumor volume and (creatine + choline)/citrate ratio may justify the initiation of voxel-specific dose escalation. This is an example of biologically motivated focal treatment for which intensity-modulated radiotherapy and especially brachytherapy are ideally suited.

J-difference lactate editing at 3.0 Tesla in the presence of strong lipids.

PURPOSE: To implement in vivo detection of lactate in the presence of lipids by proton magnetic resonance spectroscopy at a 3 Tesla (T) field strength for potential applications in human tumors outside of the brain. MATERIALS AND METHODS: The BASING J-difference sequence was implemented in the presence of high lipid concentrations in phantoms and in vivo at 3 Tesla. RESULTS: The effectiveness of the lactate editing scheme is demonstrated in phantoms containing both lactate and lipids and in vivo in ischemic induced human muscle. CONCLUSION: The ability of the BASING J-difference technique to detect lactate in the presence of strong lipid signals outside the brain at 3T is feasible. This robust technique should permit noninvasive lactate measurements in human tumors to investigate its potential as a prognostic indicator.

1H magnetic resonance spectroscopy of prostate cancer: biomarkers for tumor characterization.

Proton Magnetic Resonance Spectroscopic Imaging (MRSI) permits a non-invasive assessment of metabolites in the prostate gland. This article reviews the assessment of choline-containing compounds, citrate, and polyamines as markers for prostate tumor detection and aggressiveness.

Imaging transgene activity in vivo.

The successful translation of gene therapy for clinical application will require the assessment of transgene activity as a measure of the biological function of a therapeutic transgene. Although current imaging permits the noninvasive detection of transgene expression, the critical need for quantitative imaging of the action of the expressed transgene has not been met. In vivo magnetic resonance spectroscopic imaging (MRSI) was applied to quantitatively delineate both the concentration and activity of a cytosine deaminase-uracil phosphoribosyltransferase (CD-UPRT) fusion enzyme expressed from a transgene. MRSI enabled the generation of anatomically accurate maps of the intratumoral heterogeneity in fusion enzyme activity. We observed an excellent association between the CD-UPRT concentration and activity and the percentage of CD-UPRT(+) cells. Moreover, the regional levels of UPRT activity, as measured by imaging, correlated well with the biological affect of the enzyme. This study presents a translational imaging paradigm for precise, in vivo measurements of transgene activity with potential applications in both preclinical and clinical settings.