Search tips
Search criteria

Results 1-18 (18)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
1.  Noninvasive phosphorus magnetic resonance spectroscopic imaging predicts outcome to first-line chemotherapy in newly diagnosed patients with diffuse large B-cell lymphoma 
Academic radiology  2013;20(9):10.1016/j.acra.2013.04.013.
Rationale and Objectives
Based on their association with malignant proliferation, using noninvasive phosphorus MR spectroscopic imaging (31P MRSI), we measured the tumor content of the phospholipid-related phosphomonoesters (PME), phosphoethanolamine and phosphocholine and its correlation with treatment outcome in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients receiving standard first-line chemotherapy.
Experimental Design
The PME value normalized to nucleoside triphosphates (PME/NTP) was measured using 31P MRSI in tumor masses of 20 DLBCL patients prior to receive standard first-line chemotherapy. Response at six months was complete in 13 patients and partial in seven. Time to treatment failure (TTF) was ≤11 months in eight patients, from 18 to 30 months in three, and ≥ 60 months in nine.
On a t-test, the pretreatment tumor PME/NTP mean value (SD, n) of patients with a complete response at six months was 1.42 (0.41, 13), which was significantly different from the value of 2.46 (0.40, 7) in patients with partial response (p < 0.00001). A Fisher test significantly correlated the PME/NTP values with response at six months (sensitivity and specificity at 0.85, p < 0.004) while a Cox proportional hazards regression significantly correlated the PME/NTP values with TTF (hazard ratio=5.21, p < 0.02). A Kaplan-Meier test set apart a group entirely composed of patients with TTF ≤ 11 months (hazard ratio=8.66, p<0.00001).
The pretreatment tumor PME/NTP values correlated with response to treatment at six months and time to treatment failure in newly diagnosed DLBCL patients treated with first-line chemotherapy and therefore they could be used to predict treatment outcome in these patients.
PMCID: PMC3810177  PMID: 23931426
In vivo; lymphoma; metabolic imaging; MR spectroscopy; prediction of therapy outcome
2.  Comparing primary tumors and metastatic nodes in head and neck cancer using intravoxel incoherent motion imaging: a preliminary experience 
Journal of computer assisted tomography  2013;37(3):10.1097/RCT.0b013e318282d935.
To use intravoxel incoherent motion (IVIM) imaging for investigating differences between primary head and neck tumors and nodal metastases and evaluating IVIM efficacy in predicting outcome.
Sixteen patients with HN cancer underwent IVIM DWI on a 1.5T MRI scanner. The significance of parametric difference between primary tumors and metastatic nodes were tested. Probabilities of progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.
In comparison to metastatic nodes, the primary tumors had significantly higher vascular volume fraction (f) (p<0.0009), and lower diffusion coefficient (D) (p<0.0002). Patients with lower standard deviation for D had prolonged PFS and OS (p<0.05).
Pretreatment IVIM measures were feasible in investigating the physiological differences between the two tumor tissues. After appropriate validation, these findings might be useful in optimizing treatment planning and improving patient care.
PMCID: PMC3655331  PMID: 23674004
Intravoxel incoherent motion imaging (IVIM); head and neck (HN) cancer; primary tumor; metastatic neck node
3.  Serial measurement of hepatic lipids during chemotherapy in colorectal cancer patients: A 1H magnetic resonance spectroscopy study 
NMR in biomedicine  2012;26(2):204-212.
Background and Rationale
Hepatic steatosis is a hallmark of chemotherapy-induced liver injury. We made serial 1H magnetic resonance spectroscopy (MRS) measurements of hepatic lipids in patients over the time course of a 24-week chemotherapy regimen to determine whether 1H MRS can be used to monitor the progression of chemotherapy-induced steatosis.
Experimental Procedures
Thirty-four patients with stage III or IV colorectal cancer receiving FOLFOX (n = 21) or hepatic arterial infusion of floxuridine with systemic irinotecan (n=13) were studied prospectively. 1H MRS studies were performed at baseline and after 6 and 24 weeks of treatment. A 1H 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 (HTGC). The methodology was histologically validated in 18 patients and reproducibility was assessed in 16 normal volunteers.
Twenty-seven patients completed baseline, 6-week and 24-week 1H-MRS exams 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 non-steatotic liver. Patients whose six-week hepatic lipid levels had increased significantly compared to baseline had a high probability of lipid elevation relative to baseline at the completion of treatment as well.
Serial 1H-MRS is effective for monitoring HTGC changes during chemotherapy and detecting chemotherapy-associated steatosis. Six of 26 patients developed steatosis during chemotherapy. Lipid changes were observable at 6 weeks.
PMCID: PMC3519948  PMID: 22961714
fat; liver; FOLFOX; steatosis; imaging
4.  Extension of the Intravoxel Incoherent Motion Model to Non-Gaussian Diffusion in Head and Neck Cancer 
To extend the intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) model to restricted diffusion and to simultaneously quantify the perfusion and restricted diffusion parameters in neck nodal metastases.
Materials and Methods
The non-Gaussian (NG)-IVIM model was developed and tested on diffusion-weighted MRI data collected on a 1.5-Tesla MRI scanner from 8 patients with head and neck cancer. Voxel-wise parameter quantification was performed by using a noise-rectified least-square fitting method. The NG-IVIM, IVIM, Kurtosis, and ADC (apparent diffusion coefficient) models were used for comparison. For each voxel, within the metastatic node, the optimal model was determined using the Bayesian Information Criterion. The voxel percentage preferred by each model was calculated and the optimal model map was generated. Monte Carlo simulations were performed to evaluate the accuracy and precision dependency of the new model.
For the 8 neck nodes, the range of voxel percentage preferred by the NG-IVIM model was 2.3% - 79.3%. The optimal modal maps showed heterogeneities within the tumors. The Monte Carlo simulations demonstrated that the accuracy and precision of the NG-IVIM model improved by increasing signal-to-noise ratio and b value.
The NG-IVIM model characterizes perfusion and restricted diffusion simultaneously in neck nodal metastases.
PMCID: PMC3482143  PMID: 22826198
Intravoxel incoherent motion; noise rectification; restricted diffusion; perfusion
5.  Correlation of a priori DCE-MRI and 1H-MRS data with molecular markers in neck nodal metastases: Initial analysis 
Oral oncology  2012;48(8):717-722.
The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [1H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients.
Materials and Methods
Pretreatment DCE-MRI and 1H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the “endogenous marker” of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1α), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, 1H-MRS, and molecular marker data.
A significant correlation was observed between DCE-MRI parameter std(kep) and VEGF IHC expression level (rho = 0.81, p = 0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(Ktrans) and std(ve) (rho = −0.71; p = 0.004, and rho = −0.73; p = 0.003, respectively). Other DCE-MRI, 1H-MRS and IHC values did not show significant correlation.
The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings.
PMCID: PMC3368067  PMID: 22366441
Head and neck squamous cell carcinoma; 1H-MRS; DCE-MRI; molecular markers
6.  The Incremental Value of Contrast-Enhanced MRI in the Detection of Biopsy-Proven Local Recurrence of Prostate Cancer After Radical Prostatectomy: Effect of Reader Experience 
The purpose of this study is to retrospectively assess the incremental value of contrast-enhanced MRI (CE-MRI) to T2-weighted MRI in the detection of postsurgical local recurrence of prostate cancer by readers of different experience levels, using biopsy as the reference standard.
Fifty-two men with biochemical recurrence after prostatectomy underwent 1.5-T endorectal MRI with multiphase contrast-enhanced imaging and had biopsy within 3 months of MRI. Two radiologists (reader 1 had 1 year and reader 2 had 6 years of experience) independently reviewed each MRI study and classified the likelihood of recurrent cancer on a 5-point scale. Areas under receiver operating characteristic curves (Az) were calculated to assess readers’ diagnostic performance with T2-weighted MRI alone and combined with CE-MRI. Interobserver agreement was assessed using Cohen kappa statistics.
Thirty-three patients (63%) had biopsy-proven local recurrence of prostate cancer. With the addition of CE-MRI to T2-weighted imaging, the Az for cancer detection increased significantly for reader 1 (0.77 vs 0.85; p = 0.0435) but not for reader 2 (0.86 vs 0.88; p = 0.7294). The use of CE-MRI improved interobserver agreement from fair (κ = 0.39) to moderate (κ = 0.58).
CE-MRI increased interobserver agreement and offered incremental value to T2-weighted MRI in the detection of locally recurrent prostate cancer for the relatively inexperienced reader.
PMCID: PMC3462075  PMID: 22826397
contrast-enhanced MRI; locally recurrent prostate cancer; MRI; prostate cancer; prostatectomy
7.  Preoperative nomograms incorporating magnetic resonance imaging and spectroscopy for prediction of insignificant prostate cancer 
Bju International  2011;109(9):1315-1322.
• 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.
• 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.
• 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.
PMCID: PMC3270152  PMID: 21933336
magnetic resonance imaging; magnetic resonance spectroscopic imaging; nomograms; prostate neoplasms
8.  Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head and Neck Squamous Cell Carcinoma Patients with Nodal Metastases 
Dynamic contrast-enhanced-MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of the present study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery.
Methods and Materials
Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using Tofts model. DCE-MRI parameters were related to treatment outcome (progression free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD) or dead of other causes (DOC). Prognostic significance was assessed using the log rank test for single variables and Cox proportional hazards regression for combinations of variables.
At last clinical follow-up, for stage III, all 12 pts were NED, for stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. Ktrans is volume transfer constant. In a stepwise Cox regression skewness of Ktrans was the strongest predictor for stage IV patients (PFS and OS: p<0.001).
Our study shows that skewness of Ktrans was the strongest predictor of PFS and OS in stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter Ktrans as a predictor of outcome in these patients.
PMCID: PMC3177034  PMID: 21601373
Dynamic Contrast Enhanced-MRI (DCE-MRI); head and neck squamous cell carcinoma (HNSCC); volume transfer constant (Ktrans)
9.  Tumor Metabolism and Perfusion in Head and Neck Squamous Cell Carcinoma: Pretreatment Multimodality Imaging with 1H-Magnetic Resonance Spectroscopy, Dynamic Contrast-Enhanced MRI and 18F-FDG PET 
To correlate proton magnetic resonance spectroscopy (1H-MRS), dynamic contrast-enhanced MRI (DCE-MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in nodal metastases of patients with head and neck squamous cell carcinoma (HNSCC) for assessment of tumor biology. Additionally, pretreatment multimodality imaging (MMI) was evaluated for its efficacy in predicting short-term response to treatment.
Methods and Materials
Metastatic neck nodes were imaged with 1H-MRS, DCE-MRI and 18F-FDG PET in 16 patients with newly diagnosed HNSCC before treatment. Short-term radiological response was evaluated at 3–4 months. The correlations between 1H-MRS (choline concentration, Cho/W), DCE-MRI (volume transfer constant, Ktrans; volume fraction of the extravascular extracellular space, ve; and redistribution rate constant, kep) and 18F-FDG PET (standard uptake value, SUV; and total lesion glycolysis, TLG) were calculated using non-parametric Spearman rank correlation. To predict the short-term response, logistic regression analysis was performed.
A significant positive correlation was found between Cho/W and TLG (ρ = 0.599, p = 0.031). Cho/W correlated negatively with heterogeneity measures std(ve) (ρ = −0.691, p = 0.004) and std(kep) (ρ = −0.704, p = 0.003). SUVmax values correlated strongly with MRI tumor volume (ρ = 0.643, p = 0.007). Logistic regression indicated that std(Ktrans) and SUVmean were significant predictors of short-term response (p < 0.07).
Pretreatment multi-modality imaging using 1H-MRS, DCE-MRI and 18F-FDG PET is feasible in HNSCC patients with nodal metastases. Additionally, combined DCE-MRI and 18F-FDG PET parameters were predictive of short-term response to treatment.
PMCID: PMC3137671  PMID: 21236594
Head and neck squamous cell carcinoma; 1H-MRS; DCE-MRI; 18F-FDG PET; short-term treatment response
10.  31P-Magnetic Resonance Spectroscopic Imaging Detects Regenerative Changes in Human Liver Stimulated by Portal Vein Embolization 
First, to evaluate hepatocyte phospholipid metabolism and energetics during liver regeneration stimulated by portal vein embolization (PVE) using proton-decoupled 31P-magnetic resonance spectroscopic imaging (31P-MRSI). Second, to compare the biophysiologic differences between hepatic regeneration stimulated by PVE and by partial hepatectomy.
Materials and Methods
Subjects included 6 patients with hepatic metastases from colorectal cancer who were scheduled to undergo right PVE before definitive resection of right-sided tumor. 31P-MRSI was performed on the left liver lobe prior to PVE and 48 hours following PVE. Normalized quantities of phosphorus-containing hepatic metabolites were analyzed from both visits. In addition, MRSI data at 48 hours following partial hepatectomy were compared with the data from the PVE patients.
At 48 hours after PVE, the ratio of phosphomonoesters to phosphodiesters in the non-embolized lobe was significantly elevated. No significant changes were found in NTP and Pi values. The PME to PDE ratio in regenerating liver 48 hours after partial hepatectomy was significantly greater than PME/PDE 48 hours after PVE.
31P-MRSI is a valid technique to noninvasively evaluate cell membrane metabolism following PVE. The different degree of biochemical change between PH and PVE indicates that hepatic growth following these two procedures does not follow the same course.
PMCID: PMC3146030  PMID: 21780228
spectroscopy; phosphorus; liver; regeneration; portal vein embolization
11.  An exploratory study of endorectal MRI and spectroscopy of the prostate as pre-operative predictive biomarkers of biochemical relapse after radical prostatectomy 
The Journal of urology  2010;184(6):2320-2327.
Radical prostatectomy (RP)has significant side effects. Pre-operative information which could predict the long-term outcome of RP would be valuable to both patient and physician. The purpose of this study was to determine whether pre-treatment endorectal MRI/MRSI has the potential to predict biochemical recurrence (BCR) after RP.
Materials and Methods
130 of 202 patients who had endorectal MRI/MRSI from January 2000 to December 2002 followed by RP satisfied all inclusion criteria and were included in the analysis. MRI and MRSI factors with potential predictive capability were compared to BCR data. These included MRI risk score based on local extent of disease, and MRSI index lesion characteristics including the number of voxels and degree of metabolic abnormality (MRSI grade). Associations between MRI and MRSI variables and time-to-BCR were evaluated using Cox Proportional Hazards regression, adjusting for known predictors of BCR such as stage, grade, and PSA.
Within a median followup period of 68 months, there were 26 biochemical failures. MRI risk score, MRSI index lesion volume and presence of high grade voxels each correlated with time-to-BCR. In a model which combined clinical parameters, MRI score, MRSI lesion volume and the presence of at least one high grade voxel, the MRSI variables remained significant whereas the MRI score dropped out.
MRSI index lesion volume and the presence of high grade MRSI voxels correlate with time-to-BCR after radical prostatectomy even when adjusted for clinical data. These results suggest pre-operative predictive utility for endorectal MRI/MRSI in patients considering radical prostatectomy.
PMCID: PMC3074584  PMID: 20952035
MRI; spectroscopy; prostate; cancer; recurrence
12.  Predicting Post-External-beam Radiation Therapy PSA Relapse of Prostate Cancer Using Pre-treatment MRI 
To investigate whether pre-treatment endorectal magnetic resonance imaging (MRI) findings can predict biochemical relapse in patients with clinically localized prostate cancer (PCa) treated with external-beam radiation therapy (EBRT).
Patients and Methods
Between January 2000 and January 2002, 224 patients (median age 69 years, range 45-82) with biopsy-proven PCa underwent endorectal MRI before high-dose (≥ 81 Gy) EBRT. The value of multiple clinical and MRI variables in predicting PSA relapse at 5 years was determined using univariate and multivariate stepwise Cox regression. Clinical variables included pre-treatment PSA, clinical T-stage, Gleason score, use of neoadjuvant hormonal therapy and radiation dose. MRI variables, derived from retrospective consensus readings by two radiologists, measured intraprostatic and extraprostatic tumor burden.
After median follow-up of 67 months, 37 patients (16.5%) developed PSA relapse. The significant predictors of PSA relapse in univariate analysis were pre-treatment PSA, clinical T-stage, and multiple MRI variables including MRI TN-stage score; extracapsular extension (ECE) status; number of sextants involved by ECE, all lesions, or index (dominant) lesion; apical involvement; and diameter and volume of index lesion. Pretreatment PSA and ECE status were the only significant independent predictors upon multivariate analysis (P< 0.05 for both). ECE status was associated with the highest hazard ratio of 3.04; 5-year PSA relapse rates were 7% for no ECE, 20% for unilateral ECE, and 48% for bilateral ECE.
MRI findings can be used to predict post-EBRT PSA relapse, with ECE status on MRI and pre-treatment PSA being significant independent predictors of this endpoint.
PMCID: PMC2891893  PMID: 20133067
MR imaging; prostate cancer; external beam radiation therapy; biochemical recurrence; extracapsular extension
13.  Noninvasive assessment of tumor microenvironment using dynamic contrast enhanced MRI and 18F- fluoromisonidazole PET imaging in neck nodal metastases 
Pretreatment multimodality imaging can provide useful anatomical and functional data about tumors, including perfusion and possibly hypoxia status. The purpose of our study was to assess non-invasively the tumor microenvironment of neck nodal metastases in patients with head and neck (HN) cancer by investigating the relationship between tumor perfusion measured using Dynamic Contrast Enhanced MRI (DCE-MRI) and hypoxia measured by 18F-fluoromisonidazole (18F-FMISO) PET.
Methods and Materials
Thirteen newly diagnosed HN cancer patients with metastatic neck nodes underwent DCE-MRI and 18F-FMISO PET imaging prior to chemotherapy and radiation therapy. The matched regions of interests from both modalities were analyzed. To examine the correlations between DCE-MRI parameters and standard uptake value (SUV) measurements from 18F-FMISO PET, the non-parametric Spearman correlation coefficient was calculated. Furthermore, DCE-MRI parameters were compared between nodes with 18F-FMISO uptake and nodes with no 18F-FMISO uptake using Mann-Whitney U tests.
For the 13 patients, a total of 18 nodes were analyzed. The nodal size strongly correlated with the 18F-FMISO SUV (ρ=0.74, p<0.001). There was a strong negative correlation between the median kep (ρ=−0.58, p=0.042) and the 18F-FMISO SUV. Hypoxic nodes (moderate to severe 18F-FMISO uptake) had significantly lower median Ktrans (p=0.049) and median kep (p=0.027) values than did non-hypoxic nodes (no 18F-FMISO uptake).
This initial evaluation of the preliminary results support the hypothesis that in metastatic neck lymph nodes, hypoxic nodes are poorly perfused (i.e., have significantly lower kep and Ktrans values) compared to non-hypoxic nodes.
PMCID: PMC2888682  PMID: 19906496
Dynamic Contrast Enhanced-MRI (DCE-MRI); 18F-fluoromisonidazole (FMISO) PET; 18F-fluorodeoxyglucose (FDG); head and neck (HN) cancer
14.  Non-invasive imaging of angiogenesis in head and neck squamous cell carcinoma 
Angiogenesis  2010;13(2):149-160.
Squamous cell carcinoma of the head and neck (HNSCC) is the seventh most common cancer in the United States. Angiogenesis, the process by which new blood vessels are formed, is an essential element at the basis of both tumor growth and metastases. This review discusses pertinent aspects of the role of imaging modalities in assessing angiogenesis and anti-angiogenic therapy in advanced HNSCC.
PMCID: PMC2912423  PMID: 20383743
Head and neck squamous cell carcinoma; Angiogenesis; Anti-angiogenic treatment; Imaging techniques; Magnetic resonance imaging; Computed tomography; Positron emission tomography; Ultrasound; Molecular imaging
15.  Prediction of Prostate Cancer Recurrence Using Magnetic Resonance Imaging and Molecular Profiles 
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.
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.
MRI/MRSI findings and molecular markers correlated well with each other and contributed incremental value to clinical variables in predicting prostate cancer recurrence.
PMCID: PMC2811524  PMID: 19435838
16.  Regarding the focal treatment of prostate cancer: Inference of the Gleason grade from MR spectroscopic imaging 
The question of whether magnetic resonance spectroscopic imaging (MRSI) can be used to predict the Gleason score has been recently examined at our institution (1) and higher Gleason grade was associated with higher R=(choline+creatine)/citrate values. We wish to quantify this correlation by calculating as a function of R the probability that a particular voxel has a pathologic Gleason score ≥4+3, with sextant biopsy BxG and lesion volume V as cofactors.
Methods and Materials
The data consist of MRSI ratios R stratified by patient, lesion (contiguous abnormal voxels), voxels, biopsy and pathologic Gleason, and lesion volume. The data were analyzed using a logistic model.
For both low- and high-Gleason 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.
In patients with biopsy Gleason score ≥4+3, high MRSI tumor volume and (Cho+Cr)/Cit may justify the initiation of voxel-specific dose escalation. This is an example of biologically-motivated focal treatment for which IMRT and especially brachytherapy are ideally suited.
PMCID: PMC2692099  PMID: 18990509
prostate cancer; focal treatment; magnetic resonance spectroscopic imaging; Gleason grade
17.  Average arterial input function for quantitative dynamic contrast enhanced magnetic resonance imaging of neck nodal metastases 
The present study determines the feasibility of generating an average arterial input function (Avg-AIF) from a limited population of patients with neck nodal metastases to be used for pharmacokinetic modeling of dynamic contrast-enhanced MRI (DCE-MRI) data in clinical trials of larger populations.
Twenty patients (mean age 50 years [range 27–77 years]) with neck nodal metastases underwent pretreatment DCE-MRI studies with a temporal resolution of 3.75 to 7.5 sec on a 1.5T clinical MRI scanner. Eleven individual AIFs (Ind-AIFs) met the criteria of expected enhancement pattern and were used to generate Avg-AIF. Tofts model was used to calculate pharmacokinetic DCE-MRI parameters. Bland-Altman plots and paired Student t-tests were used to describe significant differences between the pharmacokinetic parameters obtained from individual and average AIFs.
Ind-AIFs obtained from eleven patients were used to calculate the Avg-AIF. No overall significant difference (bias) was observed for the transfer constant (Ktrans) measured with Ind-AIFs compared to Avg-AIF (p = 0.20 for region-of-interest (ROI) analysis and p = 0.18 for histogram median analysis). Similarly, no overall significant difference was observed for interstitial fluid space volume fraction (ve) measured with Ind-AIFs compared to Avg-AIF (p = 0.48 for ROI analysis and p = 0.93 for histogram median analysis). However, the Bland-Altman plot suggests that as Ktrans increases, the Ind-AIF estimates tend to become proportionally higher than the Avg-AIF estimates.
We found no statistically significant overall bias in Ktrans or ve estimates derived from Avg-AIF, generated from a limited population, as compared with Ind-AIFs.
However, further study is needed to determine whether calibration is needed across the range of Ktrans. The Avg-AIF obtained from a limited population may be used for pharmacokinetic modeling of DCE-MRI data in larger population studies with neck nodal metastases. Further validation of the Avg-AIF approach with a larger population and in multiple regions is desirable.
PMCID: PMC2679707  PMID: 19351382
18.  Prostate Cancer: Correlation of MR Imaging and MR Spectroscopy with Pathologic Findings after Radiation Therapy—Initial Experience1 
Radiology  2005;236(2):545-553.
To prospectively evaluate magnetic resonance (MR) imaging and MR spectroscopy for depiction of local prostate cancer recurrence after external-beam radiation therapy, with step-section pathologic findings as the standard of reference.
Study received institutional approval, and written informed consent was obtained. Study was compliant with Health Insurance Portability and Accountability Act. Sextant biopsy, digital rectal examination, MR imaging, MR spectroscopy, and salvage radical prostatectomy with step-section pathologic examination were performed in nine patients with increasing prostate-specific antigen levels after external-beam radiation therapy. MR imaging criterion for tumor was a focal nodular region of reduced signal intensity at T2-weighted imaging. MR spectroscopic criteria for tumor were voxels with choline (Cho) plus creatine (Cr) to citrate (Cit) ratio ([Cho + Cr]/Cit) of at least 0.5 or voxels with detectable Cho and no Cit in the peripheral zone. Sensitivity and specificity of sextant biopsy, digital rectal examination, MR imaging, and MR spectroscopy were determined by using a prostate sextant as the unit of analysis. For feature analysis, MR imaging and MR spectroscopic findings were correlated with step-section pathologic findings.
MR imaging and MR spectroscopy showed estimated sensitivities of 68% and 77%, respectively, while sensitivities of biopsy and digital rectal examination were 48% and 16%, respectively. MR spectroscopy appears to be less specific (78%) than the other three tests, each of which had a specificity higher than 90%. MR spectroscopic feature analysis showed that a metabolically altered benign gland could be falsely identified as tumor by using MR spectroscopic criteria; further analysis of MR spectroscopic features did not lead to improved MR spectroscopic criteria for recurrent tumor.
In summary, MR imaging and MR spectroscopy may be more sensitive than sextant biopsy and digital rectal examination for sextant localization of cancer recurrence after external-beam radiation therapy.
PMCID: PMC2373272  PMID: 15972335

Results 1-18 (18)