Publications by authors named "Yousef Mazaheri"

59 Publications

Multi-Site Concordance of Diffusion-Weighted Imaging Quantification for Assessing Prostate Cancer Aggressiveness.

J Magn Reson Imaging 2021 Nov 12. Epub 2021 Nov 12.

Department of Radiology, Neurology, and Radiation Oncology, University of Washington, Seattle, Washington, USA.

Background: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease.

Purpose: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms.

Study Type: Prospective.

Population: Thirty-three patients prospectively imaged prior to prostatectomy.

Field Strength/sequence: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence.

Assessment: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC).

Statistical Test: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant.

Results: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size.

Data Conclusion: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer.

Level Of Evidence: 1 TECHNICAL EFFICACY: Stage 3.
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http://dx.doi.org/10.1002/jmri.27983DOI Listing
November 2021

Diffusion-weighted MRI and histogram analysis: assessment of response to neoadjuvant chemotherapy in nephroblastoma.

Abdom Radiol (NY) 2021 07 12;46(7):3317-3325. Epub 2021 Mar 12.

Department of Radiology, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Purpose: To assess the value of diffusion-weighted MRI (DW-MRI) in the non-invasive prediction of blastemal remnant after neoadjuvant chemotherapy in nephroblastoma.

Methods: This IRB-approved study included 32 pediatric patients with 35 tumors who underwent DW-MRI prior and after completion of neoadjuvant chemotherapy and subsequent surgical resection. Two blinded radiologists volumetrically assessed each tumor on pre- and post-neoadjuvant images and the parameters mean ADC, median ADC, 12.5th/25th/75th ADC percentile, skewness, and kurtosis were calculated. Blastemal remnant was determined per the pathology report. Associations between imaging features and blastemal remnant quartiles were examined using the Kruskal-Wallis test and adjusted for false discovery rate.

Results: Inter-reader agreement was high for mean ADC, skewness, kurtosis, and volume (ICC: 0.76-0.998). Pre-therapeutic histogram parameters skewness and kurtosis were found to be higher in patients with a higher amount of blastemal remnant for reader 1 (overall p = 0.035) and for kurtosis in reader 2 (overall p = 0.032) with skewness not reaching the level of statistical significance (overall p = 0.055). Higher tumor volume on pre-treatment imaging was associated with a higher amount of blastemal remnant after therapy (overall p = 0.032 for both readers).

Conclusions: Pre-treatment skewness and kurtosis of ADC histogram analysis were significantly associated with a larger fraction of a blastemal remnant after neoadjuvant chemotherapy. These findings could be incorporated into a more personalized chemotherapeutic regime in these patients and offer prognostic information at the time of initial diagnosis.
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http://dx.doi.org/10.1007/s00261-021-03032-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215031PMC
July 2021

Magnetic resonance spectroscopic imaging in gliomas: clinical diagnosis and radiotherapy planning.

BJR Open 2020 6;2(1):20190026. Epub 2020 Apr 6.

Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA.

The reprogramming of cellular metabolism is a hallmark of cancer diagnosis and prognosis. Proton magnetic resonance spectroscopic imaging (MRSI) is a non-invasive diagnostic technique for investigating brain metabolism to establish cancer diagnosis and gene mutation diagnosis as well as facilitate pre-operative planning and treatment response monitoring. By allowing tissue metabolism to be quantified, MRSI provides added value to conventional MRI. MRSI can generate metabolite maps from a single volume or multiple volume elements within the whole brain. Metabolites such as NAA, Cho and Cr, as well as their ratios Cho:NAA ratio and Cho:Cr ratio, have been used to provide tumor diagnosis and aid in radiation therapy planning as well as treatment assessment. In addition to these common metabolites, 2-hydroxygluterate (2HG) has also been quantified using MRSI following the recent discovery of mutations in gliomas. This has opened up targeted drug development to inhibit the mutant pathway. This review provides guidance on MRSI in brain gliomas, including its acquisition, analysis methods, and evolving clinical applications.
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http://dx.doi.org/10.1259/bjro.20190026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594883PMC
April 2020

Accelerating Prostate Diffusion-weighted MRI Using a Guided Denoising Convolutional Neural Network: Retrospective Feasibility Study.

Radiol Artif Intell 2020 Aug 26;2(5):e200007. Epub 2020 Aug 26.

Departments of Medical Physics (E.A.K., I.H., Y.M., R.O.), Radiology (E.A.A., C.D., R.O., H.A.V., O.A.), and Epidemiology and Biostatistics (Z.Z.), Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room S1212B, New York, NY 10065; Institute of Computer Graphics and Vision, Graz University of Technology, Graz, Austria (E.K.); and MR Applications & Workflow Team, GE Healthcare, Chicago, Ill (M.M.F.).

Purpose: To investigate the feasibility of accelerating prostate diffusion-weighted imaging (DWI) by reducing the number of acquired averages and denoising the resulting image using a proposed guided denoising convolutional neural network (DnCNN).

Materials And Methods: Raw data from the prostate DWI scans were retrospectively gathered between July 2018 and July 2019 from six single-vendor MRI scanners. There were 103 datasets used for training (median age, 64 years; interquartile range [IQR], 11), 15 for validation (median age, 68 years; IQR, 12), and 37 for testing (median age, 64 years; IQR, 12). High -value diffusion-weighted (hb DW) data were reconstructed into noisy images using two averages and reference images using all 16 averages. A conventional DnCNN was modified into a guided DnCNN, which uses the low -value DW image as a guidance input. Quantitative and qualitative reader evaluations were performed on the denoised hb DW images. A cumulative link mixed regression model was used to compare the readers' scores. The agreement between the apparent diffusion coefficient (ADC) maps (denoised vs reference) was analyzed using Bland-Altman analysis.

Results: Compared with the original DnCNN, the guided DnCNN produced denoised hb DW images with higher peak signal-to-noise ratio (32.79 ± 3.64 [standard deviation] vs 33.74 ± 3.64), higher structural similarity index (0.92 ± 0.05 vs 0.93 ± 0.04), and lower normalized mean square error (3.9% ± 10 vs 1.6% ± 1.5) ( < .001 for all). Compared with the reference images, the denoised images received higher image quality scores from the readers ( < .0001). The ADC values based on the denoised hb DW images were in good agreement with the reference ADC values (mean ADC difference ranged from -0.04 to 0.02 × 10 mm/sec).

Conclusion: Accelerating prostate DWI by reducing the number of acquired averages and denoising the resulting image using the proposed guided DnCNN is technically feasible. © RSNA, 2020.
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http://dx.doi.org/10.1148/ryai.2020200007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529434PMC
August 2020

Diffusion-Weighted Echo Planar Imaging using MUltiplexed Sensitivity Encoding and Reverse Polarity Gradient in Head and Neck Cancer: An Initial Study.

Tomography 2020 06;6(2):231-240

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY.

We aimed to compare the geometric distortion (GD) correction performance and apparent diffusion coefficient (ADC) measurements of single-shot diffusion-weighted echo-planar imaging (SS-DWEPI), multiplexed sensitivity encoding (MUSE)-DWEPI, and MUSE-DWEPI with reverse-polarity gradient (RPG) in phantoms and patients. We performed phantom studies at 3T magnetic resonance imaging (MRI) using the American College of Radiology phantom and Quantitative Imaging Biomarker Alliance DW-MRI ice-water phantom to assess GD and effect of distortion in the measurement of ADC, respectively. Institutional review board approved the prospective clinical component of this study. DW-MRI data were obtained from 11 patients with head and neck cancer using these three DW-MRI methods. Wilcoxon signed-rank (WSR) and Kruskal-Wallis (KW) tests were used to compare ADC values, and qualitative rating by radiologist between three DW-MRI methods. In the ACR phantom, GD of 0.17% was observed for the b = 0 s/mm image of the MUSE-DWEPI with RPG method compared with that of 1.53% and 2.1% of MUSE-DWEPI and SS-DWEPI, respectively; The corresponding methods root-mean-square errors were 0.58, 3.37, and 5.07 mm. WSR and KW tests showed no significant difference in the ADC measurement between these three DW-MRI methods for both healthy masseter muscles and neoplasms ( > .05). We observed improvement in spatial accuracy for MUSE-DWEPI with RPG in the head and neck region with a higher correlation (R = 0.791) compared with that for SS-DWEPI (R = 0.707) and MUSE-DWEPI (R = 0.745). MUSE-DWEPI with RPG significantly reduces the distortion compared with MUSE-DWEPI or conventional SS-DWEPI techniques, and the ADC values were similar.
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http://dx.doi.org/10.18383/j.tom.2020.00014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289242PMC
June 2020

Computational Modeling of Interstitial Fluid Pressure and Velocity in Head and Neck Cancer Based on Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Feasibility Analysis.

Tomography 2020 06;6(2):129-138

Departments of Medical Physics and.

We developed and tested the feasibility of computational fluid modeling (CFM) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for quantitative estimation of interstitial fluid pressure (IFP) and velocity (IFV) in patients with head and neck (HN) cancer with locoregional lymph node metastases. Twenty-two patients with HN cancer, with 38 lymph nodes, underwent pretreatment standard MRI, including DCE-MRI, on a 3-Tesla scanner. CFM simulation was performed with the finite element method in COMSOL Multiphysics software. The model consisted of a partial differential equation (PDE) module to generate 3D parametric IFP and IFV maps, using the Darcy equation and values (min, estimated from the extended Tofts model) to reflect fluid influx into tissue from the capillary microvasculature. The Spearman correlation (ρ) was calculated between total tumor volumes and CFM estimates of mean tumor IFP and IFV. CFM-estimated tumor IFP and IFV mean ± standard deviation for the neck nodal metastases were 1.73 ± 0.39 (kPa) and 1.82 ± 0.9 × (10 m/s), respectively. High IFP estimates corresponds to very low IFV throughout the tumor core, but IFV rises rapidly near the tumor boundary where the drop in IFP is precipitous. A significant correlation was found between pretreatment total tumor volume and CFM estimates of mean tumor IFP (ρ = 0.50, = 0.004). Future studies can validate these initial findings in larger patients with HN cancer cohorts using CFM of the tumor in concert with DCE characterization, which holds promise in radiation oncology and drug-therapy clinical trials.
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http://dx.doi.org/10.18383/j.tom.2020.00005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289251PMC
June 2020

Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy.

Nat Genet 2020 06 1;52(6):582-593. Epub 2020 Jun 1.

Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.

In metastatic cancer, the degree of heterogeneity of the tumor microenvironment (TME) and its molecular underpinnings remain largely unstudied. To characterize the tumor-immune interface at baseline and during neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (HGSOC), we performed immunogenomic analysis of treatment-naive and paired samples from before and after treatment with chemotherapy. In treatment-naive HGSOC, we found that immune-cell-excluded and inflammatory microenvironments coexist within the same individuals and within the same tumor sites, indicating ubiquitous variability in immune cell infiltration. Analysis of TME cell composition, DNA copy number, mutations and gene expression showed that immune cell exclusion was associated with amplification of Myc target genes and increased expression of canonical Wnt signaling in treatment-naive HGSOC. Following NACT, increased natural killer (NK) cell infiltration and oligoclonal expansion of T cells were detected. We demonstrate that the tumor-immune microenvironment of advanced HGSOC is intrinsically heterogeneous and that chemotherapy induces local immune activation, suggesting that chemotherapy can potentiate the immunogenicity of immune-excluded HGSOC tumors.
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http://dx.doi.org/10.1038/s41588-020-0630-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353209PMC
June 2020

Diffusion-weighted MRI in the assessment of nephroblastoma: results of a multi-center trial.

Abdom Radiol (NY) 2020 10;45(10):3202-3212

Section of Pediatric Radiology, Department of Diagnostic and Interventional Radiology, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Purpose: To assess the value of diffusion-weighted MRI in the pre-therapeutic evaluation of pediatric renal cortical tumors.

Methods: This IRB-approved, retrospective multi-center study included 122 pediatric patients with 130 renal tumors, who underwent MRI including DWI before neoadjuvant chemotherapy and nephrectomy. Two radiologists independently assessed each tumor volumetrically, and apparent diffusion coefficient (ADC) values were calculated on a voxel-wise basis, including parameters derived from histogram and texture analysis.

Results: Inter-reader agreement was excellent (ICC 0.717-0.975). For both readers, patients with locally aggressive tumor growth (SIOP 3 stage) or with metastases (M1) had significantly lower 12.5th-percentile ADC values (p ≤ 0.028) compared to those with lower-stage tumors, and the parameter energy differed significantly between patients with M1 and those with M0 status (p ≤ 0.028). Contrast and homogeneity differed significantly between benign nephroblastomatosis and malignant nephroblastoma (p ≤ 0.045, both readers). As compared to all other subtypes, the blastemal subtype demonstrated significantly higher skewness (p ≤ 0.022, both readers) and the diffuse anaplastic subtype demonstrated significantly higher 75th-percentile ADC values (p ≤ 0.042, both readers).

Conclusions: Diffusion-weighted MRI may be of value in identifying benign nephroblastomatosis and assessing nephroblastoma subtypes. Therefore, further research is warranted to assess its value in risk stratification for pediatric patients with renal tumors in the future.
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http://dx.doi.org/10.1007/s00261-020-02475-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356178PMC
October 2020

Dynamic contrast-enhanced MRI model selection for predicting tumor aggressiveness in papillary thyroid cancers.

NMR Biomed 2020 01 4;33(1):e4166. Epub 2019 Nov 4.

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA.

The purpose of this study was to identify the optimal tracer kinetic model from T -weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data and evaluate whether parameters estimated from the optimal model predict tumor aggressiveness determined from histopathology in patients with papillary thyroid carcinoma (PTC) prior to surgery. In this prospective study, 18 PTC patients underwent pretreatment DCE-MRI on a 3 T MR scanner prior to thyroidectomy. This study was approved by the institutional review board and informed consent was obtained from all patients. The two-compartment exchange model, compartmental tissue uptake model, extended Tofts model (ETM) and standard Tofts model were compared on a voxel-wise basis to determine the optimal model using the corrected Akaike information criterion (AICc) for PTC. The optimal model is the one with the lowest AICc. Statistical analysis included paired and unpaired t-tests and a one-way analysis of variance. Bonferroni correction was applied for multiple comparisons. Receiver operating characteristic (ROC) curves were generated from the optimal model parameters to differentiate PTC with and without aggressive features, and AUCs were compared. ETM performed best with the lowest AICc and the highest Akaike weight (0.44) among the four models. ETM was preferred in 44% of all 3419 voxels. The ETM estimates of K in PTCs with the aggressive feature extrathyroidal extension (ETE) were significantly higher than those without ETE (0.78 ± 0.29 vs. 0.34 ± 0.18 min , P = 0.005). From ROC analysis, cut-off values of K , v and v , which discriminated between PTCs with and without ETE, were determined at 0.45 min , 0.28 and 0.014 respectively. The sensitivities and specificities were 86 and 82% (K ), 71 and 82% (v ), and 86 and 55% (v ), respectively. Their respective AUCs were 0.90, 0.71 and 0.71. We conclude that ETM K has shown potential to classify tumors with and without aggressive ETE in patients with PTC.
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http://dx.doi.org/10.1002/nbm.4166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687051PMC
January 2020

Evaluation of diffusion kurtosis and diffusivity from baseline staging MRI as predictive biomarkers for response to neoadjuvant chemoradiation in locally advanced rectal cancer.

Abdom Radiol (NY) 2019 11;44(11):3701-3708

Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.

Purpose: To evaluate the role of diffusion kurtosis and diffusivity as potential imaging biomarkers to predict response to neoadjuvant chemoradiation therapy (CRT) from baseline staging magnetic resonance imaging (MRI) in locally advanced rectal cancer (LARC).

Materials And Methods: This retrospective study included 45 consecutive patients (31 male/14 female) who underwent baseline MRI with high b-value sequences (up to 1500 mm/s) for LARC followed by neoadjuvant chemoradiation and surgical resection. The mean age was 57.4 years (range 34.2-72.9). An abdominal radiologist using open source software manually segmented T2-weighted images. Segmentations were used to derive diffusion kurtosis and diffusivity from diffusion-weighted images as well as volumetric data. These data were analyzed with regard to tumor regression grade (TRG) using the four-tier American Joint Committee on Cancer (AJCC) classification, TRG 0-3. Proportional odds regression was used to analyze the four-level ordinal outcome. A sensitivity analysis was performed using univariable logistic regression for binary TRG groups, TRG 0/1 (> 90% response), or TRG 2/3 (< 90% response). p < 0.05 was considered significant throughout.

Results: In the univariable proportional odds regression analysis, higher diffusivity summary (D) values were observed to be significantly associated with higher odds of being in one or more favorable TRG group (TRG 0 or 1). In other words, on average, patients with higher D values were more likely to be in a more favorable TRG group. These results are mostly consistent with the sensitivity analysis, in which higher values for most D values [all but region of interest (ROI)-max D median (p = 0.08)] were observed to be significantly associated with higher odds of being TRG 0 or 1. Tumor volume of interest (VOI) and ROI volume, ROI kurtosis mean and median, and VOI kurtosis mean and median were not significantly associated with TRG.

Conclusion: Diffusivity derived from the baseline staging MRI, but not diffusion kurtosis or volumetric data, is associated with TRG and therefore shows promise as a potential imaging biomarker to predict the response to neoadjuvant chemotherapy in LARC.

Clinical Relevance Statement: Diffusivity shows promise as a potential imaging biomarker to predict AJCC TRG following neoadjuvant CRT, which has implications for risk stratification. Patients with TRG 0/1 have 5-year disease-free survival (DFS) of 90-98%, as opposed to those who are TRG 2/3 with 5-year DFS of 68-73%.
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http://dx.doi.org/10.1007/s00261-019-02073-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457148PMC
November 2019

Quantitative Non-Gaussian Intravoxel Incoherent Motion Diffusion-Weighted Imaging Metrics and Surgical Pathology for Stratifying Tumor Aggressiveness in Papillary Thyroid Carcinomas.

Tomography 2019 03;5(1):26-35

Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY.

We assessed a priori aggressive features using quantitative diffusion-weighted imaging metrics to preclude an active surveillance management approach in patients with papillary thyroid cancer (PTC) with tumor size 1-2 cm. This prospective study enrolled 24 patients with PTC who underwent pretreatment multi-b-value diffusion-weighted imaging on a GE 3 T magnetic resonance imaging scanner. The apparent diffusion coefficient (ADC) metric was calculated from monoexponential model, and the perfusion fraction (), diffusion coefficient (), pseudo-diffusion coefficient (), and diffusion kurtosis coefficient () metrics were estimated using the non-Gaussian intravoxel incoherent motion model. Neck ultrasonography examination data were used to calculate tumor size. The receiver operating characteristic curve assessed the discriminative specificity, sensitivity, and accuracy between PTCs with and without features of tumor aggressiveness. Multivariate logistic regression analysis was performed on metrics using a leave-1-out cross-validation method. Tumor aggressiveness was defined by surgical histopathology. Tumors with aggressive features had significantly lower ADC and values than tumors without tumor-aggressive features ( < .05). The absolute relative change was 46% in metric value between the 2 tumor types. In total, 14 patients were in the critical size range (1-2 cm) measured by ultrasonography, and the ADC and were significantly different and able to differentiate between the 2 tumor types ( < .05). ADC and can distinguish tumors with aggressive histological features to preclude an active surveillance management approach in patients with PTC with tumors measuring 1-2 cm.
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http://dx.doi.org/10.18383/j.tom.2018.00054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403039PMC
March 2019

The Influence of Background Signal Intensity Changes on Cancer Detection in Prostate MRI.

AJR Am J Roentgenol 2019 04 4;212(4):823-829. Epub 2019 Feb 4.

6 Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY.

Objective: The objective of this study was to develop a scoring system for background signal intensity changes or prostate homogeneity on prostate MRI and to assess these changes' influence on cancer detection.

Materials And Methods: This institutional review board-approved, HIPAA-compliant, retrospective study included 418 prostate MRI examinations in 385 men who subsequently underwent MRI-guided biopsy. The Likert score for suspicion of cancer assigned by the primary radiologist was extracted from the original report, and histopathologic work-up of the biopsy cores served as the reference standard. Two readers assessed the amount of changes on T2-weighted sequences and assigned a predefined prostate signal-intensity homogeneity score of 1-5 (1 = poor, extensive changes; 5 = excellent, no changes). The sensitivity and specificity of Likert scores for detection of prostate cancer and clinically significant cancer (Gleason score ≥ 3+4) were estimated in and compared between subgroups of patients with different signal-intensity homogeneity scores (≤ 2, 3, and ≥ 4).

Results: Interreader agreement on signal-intensity homogeneity scores was substantial (κ = 0.783). Sensitivity for prostate cancer detection increased when scores were better (i.e., higher) (reader 1, from 0.41 to 0.71; reader 2, from 0.53 to 0.73; p ≤ 0.007, both readers). In the detection of significant cancer (Gleason score ≥ 3+4), sensitivity also increased with higher signal-intensity scores (reader 1, from 0.50 to 0.82; reader 2, from 0.63 to 0.86; p ≤ 0.028), though specificity decreased significantly for one reader (from 0.67 to 0.38; p = 0.009).

Conclusion: Background signal-intensity changes on T2-weighted images significantly limit prostate cancer detection. The proposed scoring system could improve the standardization of prostate MRI reporting and provide guidance for applying prostate MRI results appropriately in clinical decision-making.
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http://dx.doi.org/10.2214/AJR.18.20295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430663PMC
April 2019

High-Signal Bladder Urine at T1-Weighted MR Imaging Performed 1-7 Days After a Prior Gadolinium-Enhanced MRI: Prevalence and Correlation with Renal Function.

BJR Open 2019 29;1(1). Epub 2019 May 29.

Departments of Radiology Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Objective: To determine the prevalence of high-signal bladder urine at T1-weighted MRI performed 1-7 days after injection of gadolinium-based contrast material and to assess for correlation with altered renal function.

Methods: The study group consisted of 267 patients who underwent MRI that included the bladder 1-7 days after a prior gadolinium-enhanced MRI. A control group consisted of 200 patients who underwent pelvic MRI and had not received gadolinium-based contrast material within the prior month. One reader recorded the relative T1-weighted signal intensity of bladder urine and calculated the eGFR for each patient. A positive scan was defined as one with bladder urine T1-weighted signal higher than that of muscle.

Results: Twenty-five (9%) of 267 study group scans were positive; this included 68% (n=19) of scans obtained 12-24 hours after gadolinium-based contrast material administration, 21% (n=3) after 25-36 hours, 7% (n=2) after 37-48 hours, and 3% (n=1) after 49-72 hours. No positive scan occurred after 72 hours or in the control group. Mean eGFR in positive scans obtained more than 36 hours after gadolinium-based contrast material administration was significantly lower than in negative scans in the same timeframe (37 ml/min versus 76 ml/min, respectively; p = 0.01).

Conclusion: High T1-weighted signal in bladder urine occasionally is present on MRI performed up to 3 days after gadolinium-based contrast material administration, presumably reflecting residual excreted gadolinium-based contrast material. When visible more than 36 hours after gadolinium-based contrast material administration, such increased signal is associated with decreased eGFR.

Advances In Knowledge: Increased signal is occasionally present on bladder urine MRI performed up to 3 days post gadolinium-based contrast material administration. When higher signal is visible more than 36 hours after gadolinium-based contrast material administration it is associated with decreased eGFR.
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http://dx.doi.org/10.1259/bjro.20180030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454119PMC
May 2019

Sorafenib for Advanced and Refractory Desmoid Tumors.

N Engl J Med 2018 12;379(25):2417-2428

From Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center (M.M.G., W.D.T., N.H., N.P.A., R.A.L., Y.M., R.Y.) and Columbia University Vagellos College of Physicians and Surgeons and New York Presbyterian Hospital (L.H.S., G.K.S.), New York, and Northwell Cancer Institute and Cold Spring Harbor Laboratory, Lake Success (R.G.M.) - all in New York; Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN (M.R.M.); Washington University School of Medicine, St. Louis (B.A.V.T.); M.D. Anderson Cancer Center, University of Texas, Houston (V.R.); Mayo Clinic in Florida, Jacksonville (S.A.); Yale University, New Haven, CT (H.A.D.); University Health Network Princess Margaret Cancer Centre, Toronto (A.A.G.); University of Iowa-Holden Comprehensive Cancer Center, Iowa City (M.M.M.); University of Alabama at Birmingham Cancer Center, Birmingham (R.M.C.); Fox Chase Cancer Center, Philadelphia (S.M.); Georgetown University, Lombardi Comprehensive Cancer Center, Washington, DC (M.J.P.); Duke Cancer Institute, Duke University Medical Center, Durham (R.F.R.), and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill (E.B.) - both in North Carolina; Dayton National Cancer Institute Community Oncology Research Program, Dayton, OH (T.S.); National Cancer Institute, Bethesda, MD (J.J.W.); and the Alliance Statistics and Data Center, Mayo Clinic, Scottsdale, AZ (A.C.D.).

Background: Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care.

Methods: In this double-blind, phase 3 trial, we randomly assigned 87 patients with progressive, symptomatic, or recurrent desmoid tumors to receive either sorafenib (400-mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated.

Results: With a median follow-up of 27.2 months, the 2-year progression-free survival rate was 81% (95% confidence interval [CI], 69 to 96) in the sorafenib group and 36% (95% CI, 22 to 57) in the placebo group (hazard ratio for progression or death, 0.13; 95% CI, 0.05 to 0.31; P<0.001). Before crossover, the objective response rate was 33% (95% CI, 20 to 48) in the sorafenib group and 20% (95% CI, 8 to 38) in the placebo group. The median time to an objective response among patients who had a response was 9.6 months (interquartile range, 6.6 to 16.7) in the sorafenib group and 13.3 months (interquartile range, 11.2 to 31.1) in the placebo group. The objective responses are ongoing. Among patients who received sorafenib, the most frequently reported adverse events were grade 1 or 2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%).

Conclusions: Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT02066181 .).
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http://dx.doi.org/10.1056/NEJMoa1805052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447029PMC
December 2018

Single-dose radiotherapy disables tumor cell homologous recombination via ischemia/reperfusion injury.

J Clin Invest 2019 02 14;129(2):786-801. Epub 2019 Jan 14.

Laboratory of Signal Transduction.

Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3×9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention.
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http://dx.doi.org/10.1172/JCI97631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355243PMC
February 2019

Characterization of prostate cancer with MR spectroscopic imaging and diffusion-weighted imaging at 3 Tesla.

Magn Reson Imaging 2019 01 31;55:93-102. Epub 2018 Aug 31.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose: To retrospectively measure metabolic ratios and apparent diffusion coefficient (ADC) values from 3-Tesla MR spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI) in benign and malignant peripheral zone (PZ) prostate tissue, assess the parameters' associations with malignancy, and develop and test rules for classifying benign and malignant PZ tissue using whole-mount step-section pathology as the reference standard.

Methods: This HIPAA-compliant, IRB-approved study included 67 men (median age, 61 years; range, 41-74 years) with biopsy-proven prostate cancer who underwent preoperative 3 T endorectal multiparametric MRI and had ≥1 PZ lesion >0.1 cm at whole-mount histopathology. In benign and malignant PZ regions identified from pathology, voxel-based choline/citrate, polyamines/choline, polyamines/creatine, and (choline + polyamines + creatine)/citrate ratios were averaged, as were ADC values. Patients were randomly split into training and test sets; rules for separating benign from malignant regions were generated with classification and regression tree (CART) analysis and assessed on the test set for sensitivity and specificity. Odds ratios (OR) were evaluated using generalized estimating equations.

Results: CART analysis of all parameters identified only ADC and (choline + polyamines + creatine)/citrate as significant predictors of cancer. Sensitivity and specificity, respectively, were 0.81 and 0.82 with MRSI-derived, 0.98 and 0.51 with DWI-derived, and 0.79 and 0.90 with MRSI + DWI-derived classification rules. Areas under the curves (AUC) in the test set were 0.93 (0.87-0.97) with ADC, 0.82 (0.72-0.91) with MRSI, and 0.96 (0.92-0.99) with MRSI + ADC.

Conclusion: We developed statistically-based rules for identifying PZ cancer using 3-Tesla MRSI, DWI, and MRSI + DWI and demonstrated the potential value of MRSI + DWI.
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http://dx.doi.org/10.1016/j.mri.2018.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652218PMC
January 2019

Temporal changes in MRI appearance of the prostate after focal ablation.

Abdom Radiol (NY) 2019 01;44(1):272-278

Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.

Purpose: The purpose of our study was to retrospectively evaluate and categorize temporal changes in MRI appearances of the prostate in patients who underwent focal therapy with MRI follow-up.

Methods: The Institutional Review Board approved this retrospective study and waived the requirement for informed consent. Thirty-seven patients (median age 61; 48-70 years) with low-to-intermediate-risk, clinically organ-confined prostate cancer underwent focal ablation therapy from 2009 to 2014. Two radiologists reviewed post-treatment MRIs (n = 76) and categorized imaging features blinded to the time interval between the focal therapy and the follow-up MRI. Inter-reader agreement was assessed (kappa) and generalized linear regression was used to examine associations between an imaging feature being present/absent and days between ablation and MRI.

Results: Inter-reader agreement on MRI features ranged from fair to substantial. Edema was found present at earlier times after ablation (median 16-25 days compared to MRIs without edema, median 252-514 days), as was rim enhancement of the ablation zone (18-22.5 days vs. 409-593 days), a hypointense rim around the ablation zone on T2-weighted images (53-57.5 days vs. 279-409 days) and the presence of an appreciable ablation cavity (48.5-60 days vs. 613-798 days, all p < 0.05). Enhancement of the ablation zone/scar (553-731 days vs. 61.5-162 days) and the formation of a T2-hypointense scar were found to be present on later MRI scans (514-553 days vs. 29-32 days, one reader).

Conclusions: The MRI appearance of the prostate after focal ablation changes substantially over time. Identification of temporal patterns in the appearance of imaging features should help reduce image interpretation variability and errors when assessing post-therapeutic scans.
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http://dx.doi.org/10.1007/s00261-018-1715-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894419PMC
January 2019

Effect of intravascular contrast agent on diffusion and perfusion fraction coefficients in the peripheral zone and prostate cancer.

Magn Reson Imaging 2018 09 17;51:120-127. Epub 2018 Apr 17.

Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States.

Purpose: To determine whether water diffusion and the perfusion fraction coefficients in prostate peripheral zone (PZ) and prostate cancer (PCa) are affected by intravenous contrast injection and explore the potential mechanism behind previously reported differences between pre- and post-contrast ADC values.

Methods: Our institutional review board waived informed consent for this HIPAA-compliant, retrospective study, which included 32 patients (median age, 63 years; range, 47-77 years) with biopsy-proven, untreated PCa who underwent 3-Tesla MRI, including DW-MRI at b-values 0, 400, 700, 1000 s/mm before and after gadolinium injection. For regions of interest (ROIs) in presumed benign PZ and PZ PCa, apparent diffusion coefficient (ADC), perfusion fraction f, and diffusion coefficient D were estimated voxel-wise, and signal-to-noise ratio (SNR) and contrast-to-noise (CNR) were estimated. Pre- and post-contrast measurements were compared by Wilcoxon signed-rank test; P < 0.05 was considered significant.

Results: In PZ, f (P = 0.002) was significantly higher on post-contrast imaging than on pre-contrast imaging, but ADC and D values did not change significantly (P = 0.562 and 0.295 respectively). In PCa, all parameters differed significantly between post-contrast and pre-contrast imaging (P < 0.0001 for ADC, P = 0.0084 for D, and P = 0.029 for f). On post-contrast imaging, SNR was not significantly different in PZ (P = 0.260) but was significantly lower in PCa (P < 0.0001); CNR did not change significantly (P = 0.059).

Conclusion: After contrast injection, ADC and D declined significantly in PCa only, while f increased significantly in both PCa and PZ. Pre- and post-contrast diffusion parameters cannot be used interchangeably for diagnostic purposes that require quantitative diffusion estimates.
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http://dx.doi.org/10.1016/j.mri.2018.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638580PMC
September 2018

Dynamic contrast-enhanced magnetic resonance imaging of prostate cancer: A review of current methods and applications.

World J Radiol 2017 Dec;9(12):416-425

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.

In many areas of oncology, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has proven to be a clinically useful, non-invasive functional imaging technique to quantify tumor vasculature and tumor perfusion characteristics. Tumor angiogenesis is an essential process for tumor growth, proliferation, and metastasis. Malignant lesions demonstrate rapid extravasation of contrast from the intravascular space to the capillary bed due to leaky capillaries associated with tumor neovascularity. DCE-MRI has the potential to provide information regarding blood flow, areas of hypoperfusion, and variations in endothelial permeability and microvessel density to aid treatment selection, enable frequent monitoring during treatment and assess response to targeted therapy following treatment. This review will discuss the current status of DCE-MRI in cancer imaging, with a focus on its use in imaging prostate malignancies as well as weaknesses that limit its widespread clinical use. The latest techniques for quantification of DCE-MRI parameters will be reviewed and compared.
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http://dx.doi.org/10.4329/wjr.v9.i12.416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746645PMC
December 2017

Quantitating whole lesion tumor biology in rectal cancer MRI: taking a lesson from FDG-PET tumor metrics.

Abdom Radiol (NY) 2018 07;43(7):1575-1582

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

Purpose: To determine the value of novel whole tumor metrics in DWI-MRI and DCE-MRI of rectal cancer treatment assessment.

Materials And Methods: This retrospective study included 24 uniformly treated patients with rectal adenocarcinoma who underwent MRI including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after chemoradiotherapy. Two experienced readers independently measured tumor volume and apparent diffusion coefficient (ADC) on DWI-MRI and tumor volume and transfer constant K on DCE-MRI. In addition, we explored and defined Total Lesion Diffusion (TLD) as Total DWI tumor volume multiplied by mean volumetric ADC and Total Lesion Perfusion (TLP) as the total DCE tumor volume multiplied by the mean volumetric K . These metrics were correlated with histopathologic percent tumor regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC).

Results: For both readers, post-treatment TLP revealed comparable correlations with %TR compared with K (reader 1; Spearman's rho = - 0.36 vs. - 0.32, reader 2; Spearman's rho = - 0.32 vs. - 0.28). In addition, TLP afforded the highest inter-reader agreement at post-treatment among TLP, DCE vol, and K (CCC: 0.64 vs. 0.36 vs. 0.35). Post-treatment TLD showed similar correlation with %TR as DWI volume in reader 1 and superior correlation with %TR for reader 2 (reader 1; Spearman's rho - 0.56 vs. - 0.57, reader 2; Spearman's rho - 0.59 vs. - 0.45).

Conclusion: The novel tumor metrics TLD and TLP revealed similar results to established metrics for correlation with tumor response with equivalent or superior inter-reader agreements and we recommend that these be studied in larger trials.
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http://dx.doi.org/10.1007/s00261-017-1389-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960599PMC
July 2018

Model selection for high b-value diffusion-weighted MRI of the prostate.

Magn Reson Imaging 2018 02 12;46:21-27. Epub 2017 Oct 12.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Purpose: To assess the abilities of the standard mono-exponential (ME), bi-exponential (BE), diffusion kurtosis (DK) and stretched exponential (SE) models to characterize diffusion signal in malignant and prostatic tissues and determine which of the four models best characterizes these tissues on a per-voxel basis.

Materials And Methods: This institutional-review-board-approved, HIPAA-compliant, retrospective study included 55 patients (median age, 61years; range, 42-77years) with untreated, biopsy-proven PCa who underwent endorectal coil MRI at 3-Tesla, diffusion-weighted MRI acquired at eight b-values from 0 to 2000s/mm. Estimated parameters were apparent diffusion coefficent (ME model); diffusion coefficients for the fast (D) and slow (D) components and fraction of fast component, f (BE model); diffusion coefficient D, and kurtosis K (DK model); distributed diffusion coefficient DDC and α for (SE model). For one region-of-interest (ROI) in PZ and another in PCa in each patient, the corrected Akaike information criterion (AICc) and the Akaike weight (w) were calculated for each voxel.

Results: Based on AICc and w, all non-monoexponential models outperformed the ME model in PZ and PCa. The DK model in PZ and SE model in PCa ROIs best fit the greatest average percentages of voxels (39% and 43%, respectively) and had the highest mean w (35±16×10 and 41±22×10, respectively).

Conclusion: DK and SE models best fit DWI data in PZ and PCa, and non-ME models consistently outperformed the ME model. Voxel-wise mapping of the preferential model demonstrated that the vast majority of voxels in either tissue type were best fit with one of the non-monoexponential models. At the given SNR levels, the maximum b-value of 2000s/mm is not sufficiently high to identify the preferred non-monoexponential model.
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http://dx.doi.org/10.1016/j.mri.2017.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638582PMC
February 2018

Multimodality imaging using proton magnetic resonance spectroscopic imaging and F-fluorodeoxyglucose-positron emission tomography in local prostate cancer.

World J Radiol 2017 Mar;9(3):134-142

Amita Shukla-Dave, Heiko Schöder, Yousef Mazaheri, Hedvig Hricak, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States.

Aim: To assess the relationship using multimodality imaging between intermediary citrate/choline metabolism as seen on proton magnetic resonance spectroscopic imaging (H-MRSI) and glycolysis as observed on F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) in prostate cancer (PCa) patients.

Methods: The study included 22 patients with local PCa who were referred for endorectal magnetic resonance imaging/H-MRSI (April 2002 to July 2007) and F-FDG-PET/CT and then underwent prostatectomy as primary or salvage treatment. Whole-mount step-section pathology was used as the standard of reference. We assessed the relationships between PET parameters [standardized uptake value (SUVmax and SUVmean)] and MRSI parameters [choline + creatine/citrate (CC/Cmax and CC/Cmean) and total number of suspicious voxels] using spearman's rank correlation, and the relationships of PET and H-MRSI index lesion parameters to surgical Gleason score.

Results: Abnormal intermediary metabolism on H-MRSI was present in 21/22 patients, while abnormal glycolysis on F-FDG-PET/CT was detected in only 3/22 patients. Specifically, index tumor localization rates were 0.95 (95%CI: 0.77-1.00) for H-MRSI and 0.14 (95%CI: 0.03-0.35) for F-FDG-PET/CT. Spearman rank correlations indicated little relationship (ρ = -0.36-0.28) between H-MRSI parameters and F-FDG-PET/CT parameters. Both the total number of suspicious voxels (ρ = 0.55, = 0.0099) and the SUVmax (ρ = 0.46, = 0.0366) correlated weakly with the Gleason score. No significant relationship was found between the CC/Cmax, CC/Cmean or SUVmean and the Gleason score ( = 0.15-0.79).

Conclusion: The concentration of intermediary metabolites detected by H MRSI and glycolytic flux measured F-FDG PET show little correlation. Furthermore, only few tumors were FDG avid on PET, possibly because increased glycolysis represents a late and rather ominous event in the progression of PCa.
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http://dx.doi.org/10.4329/wjr.v9.i3.134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368629PMC
March 2017

Differentiation of Clear Cell Renal Cell Carcinoma From Other Renal Cortical Tumors by Use of a Quantitative Multiparametric MRI Approach.

AJR Am J Roentgenol 2017 Mar 17;208(3):W85-W91. Epub 2017 Jan 17.

1 Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065.

Objective: The purpose of this study was to develop a quantitative multiparametric MRI approach to differentiating clear cell renal cell carcinoma (RCC) from other renal cortical tumors.

Materials And Methods: This retrospective study included 119 patients with 124 histopathologically confirmed renal cortical tumors who underwent preoperative MRI including DWI, contrast-enhanced, and chemical-shift sequences before nephrectomy. Two radiologists independently assessed each tumor volumetrically, and apparent diffusion coefficient values, parameters from multiphasic contrast-enhanced MRI (peak enhancement, upslope, downslope, AUC), and chemical-shift indexes were calculated. Univariate and multivariable logistic regression analyses were performed to identify parameters associated with clear cell RCC.

Results: Interreader agreement was excellent (intraclass correlation coefficient, 0.815-0.994). The parameters apparent diffusion coefficient (reader 1 AUC, 0.804; reader 2, 0.807), peak enhancement (reader 1 AUC, 0.629; reader 2, 0.606), and downslope (reader 1 AUC, 0.575; reader 2, 0.561) were significantly associated with discriminating clear cell RCC from other renal cortical tumors. The combination of all three parameters further increased diagnostic accuracy (reader 1 AUC, 0.889; reader 2, 0.907; both p ≤ 0.001), yielding sensitivities of 0.897 for reader 1 and 0.897 for reader 2, and specificities of 0.762 for reader 1 and 0.738 for reader 2 in the identification of clear cell RCC. With maximized sensitivity, specificities of 0.429 and 0.262 were reached for readers 1 and 2, respectively.

Conclusion: A quantitative multiparametric approach statistically significantly improves diagnostic performance in differentiating clear cell RCC from other renal cortical tumors.
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http://dx.doi.org/10.2214/AJR.16.16652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441564PMC
March 2017

Effect of immersion time on the passive and electrochemical response of annealed and nano-grained commercial pure titanium in Ringer's physiological solution at 37°C.

Mater Sci Eng C Mater Biol Appl 2017 Feb 26;71:771-779. Epub 2016 Oct 26.

Department of Mining & Materials Engineering, McGill University, Montreal, Quebec H3A 0C5, Canada.

In the present study, various electrochemical tests were used to investigate the passive and electrochemical response of annealed and nano-grained commercial pure Titanium in Ringer's physiological solution at 37°C. Nano-grained pure Titanium, which typically has an average grain size of 90±5nm, was obtained by six-cycle accumulative roll bonding process. Polarization and electrochemical impedance spectroscopy plots illustrated that as a result of grain refinement process, the passive response of the nano-grained sample was improved compared to that of its coarse-grained counterpart in Ringer's physiological solution. Mott-Schottky analysis indicated that the passive films behaved as n-type semiconductors in Ringer's physiological solution and grain refinement did not change the conductivity type of the passive films. Additionally, Mott-Schottky analysis showed that the donor density decreased by grain size reduction. Finally, nano-grained sample appeared to be more suitable for implant applications, mainly due to the formation of thicker and less defective oxide film.
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http://dx.doi.org/10.1016/j.msec.2016.10.057DOI Listing
February 2017

Multiparametric MRI in the assessment of response of rectal cancer to neoadjuvant chemoradiotherapy: A comparison of morphological, volumetric and functional MRI parameters.

Eur Radiol 2016 Dec 5;26(12):4303-4312. Epub 2016 Mar 5.

Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.

Purpose: To compare morphological and functional MRI metrics and determine which ones perform best in assessing response to neoadjuvant chemoradiotherapy (CRT) in rectal cancer.

Materials And Methods: This retrospective study included 24 uniformly-treated patients with biopsy-proven rectal adenocarcinoma who underwent MRI, including diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) sequences, before and after completion of CRT. On all MRI exams, two experienced readers independently measured longest and perpendicular tumour diameters, tumour volume, tumour regression grade (TRG) and tumour signal intensity ratio on T2-weighted imaging, as well as tumour volume and apparent diffusion coefficient on DW-MRI and tumour volume and transfer constant K on DCE-MRI. These metrics were correlated with histopathological percent tumour regression in the resected specimen (%TR). Inter-reader agreement was assessed using the concordance correlation coefficient (CCC).

Results: For both readers, post-treatment DW-MRI and DCE-MRI volumetric tumour assessments were significantly associated with %TR; DCE-MRI volumetry showed better inter-reader agreement (CCC=0.700) than DW-MRI volumetry (CCC=0.292). For one reader, mrTRG, post-treatment T2 tumour volumetry and assessments of volume change made with T2, DW-MRI and DCE-MRI were also significantly associated with %TR.

Conclusion: Tumour volumetry on post-treatment DCE-MRI and DW-MRI correlated well with %TR, with DCE-MRI volumetry demonstrating better inter-reader agreement.

Key Points: • Volumetry on post-treatment DCE-/DW-MRI sequences correlated well with histopathological tumour regression. • DCE-MRI volumetry demonstrated good inter-reader agreement. • Inter-reader agreement was higher for DCE-MRI volumetry than for DW-MRI volumetry. • DCE-MRI volumetry merits further investigation as a metric for evaluating treatment response.
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http://dx.doi.org/10.1007/s00330-016-4283-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203699PMC
December 2016

Assessment of Prostate Cancer Aggressiveness by Use of the Combination of Quantitative DWI and Dynamic Contrast-Enhanced MRI.

AJR Am J Roentgenol 2016 Apr 22;206(4):756-63. Epub 2016 Feb 22.

1 Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065.

Objective: The objective of this study was to investigate whether the apparent diffusion coefficient (ADC) value from DWI and the forward volume transfer constant (K(trans)) value from dynamic contrast-enhanced MRI independently predict prostate cancer aggressiveness, and to determine whether the combination of both parameters performs better than either parameter alone in assessing tumor aggressiveness before treatment.

Materials And Methods: This retrospective study included 158 men with histopathologically confirmed prostate cancer who underwent 3-T MRI before undergoing prostatectomy in 2011. Whole-mount step-section pathologic maps identified 195 prostate cancer foci that were 0.5 mL or larger; these foci were then volumetrically assessed to calculate the per-tumor ADC and K(trans) values. Associations between MRI and histopathologic parameters were assessed using Spearman correlation coefficients, univariate and multivariable logistic regression, and AUCs.

Results: The median ADC and K(trans) values showed moderate correlation only for tumors for which the Gleason score (GS) was 4 + 4 or higher (ρ = 0.547; p = 0.042). The tumor ADC value was statistically significantly associated with all dichotomized GSs (p < 0.005), including a GS of 3 + 3 versus a GS of 3 + 4 or higher (AUC, 0.693; p = 0.001). The tumor K(trans) value differed statistically significantly only between tumors with a GS of 3 + 3 and those with a primary Gleason grade of 4 (p ≤ 0.015), and it made a statistically significant contribution only in differentiating tumors with a GS of 4 + 3 or higher (AUC, 0.711; p < 0.001) and those with a GS of 4 + 4 or higher (AUC, 0.788; p < 0.001) from lower-grade tumors. Combining ADC and K(trans) values improved diagnostic performance in characterizing tumors with a GS of 4 + 3 or higher and those with a GS of 4 + 4 or higher (AUC, 0.739 and 0.856, respectively; p < 0.01).

Conclusion: Although the ADC value helped to differentiate between all GSs, the K(trans) value was only a benefit in characterizing more aggressive tumors. Combining these parameters improves their performance in identifying patients with aggressive tumors who may require radical treatment.
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http://dx.doi.org/10.2214/AJR.15.14912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479568PMC
April 2016

Texture analysis on parametric maps derived from dynamic contrast-enhanced magnetic resonance imaging in head and neck cancer.

World J Radiol 2016 Jan;8(1):90-7

Jacobus FA Jansen, Department of Radiology, Maastricht University Medical Center, 6211 LK Maastricht, the Netherlands.

Aim: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: In this retrospective study, 19 HNSCC patients underwent pre- and intra-treatment DCE-MRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images, generating maps of volume transfer rate (K(trans)) and volume fraction of the extravascular extracellular space (ve). Image texture analysis was then employed on maps of K(trans) and ve, generating two texture measures: Energy (E) and homogeneity.

Results: No significant changes were found for the mean and standard deviation for K(trans) and ve between pre- and intra-treatment (P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra-treatment scans, relative to pretreatment scans (P < 0.04).

Conclusion: Chemo-radiation treatment in HNSCC significantly reduces the heterogeneity of tumors.
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http://dx.doi.org/10.4329/wjr.v8.i1.90DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731352PMC
January 2016

Use of DWI in the Differentiation of Renal Cortical Tumors.

AJR Am J Roentgenol 2016 Jan;206(1):100-5

1 Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.

Objective: The purpose of this study was to differentiate clear cell renal cell carcinoma (RCC) from other common renal cortical tumors by use of DWI.

Materials And Methods: The study included 117 patients (mean age, 60 years) with 122 histopathologically confirmed renal cortical tumors who underwent 1.5-T MRI that included DWI before they underwent nephrectomy between 2006 and 2013. For each tumor, two radiologists independently evaluated apparent diffusion coefficient (ADC) values on the basis of a single ROI in a nonnecrotic area of the tumor and also by assessment of the whole tumor. The concordance correlation coefficient (CCC) was calculated to assess interreader agreement. The mean ADC values of clear cell RCC and every other tumor subtype were compared using an exact Wilcoxon rank sum test.

Results: Interreader agreement was excellent and higher in whole-tumor assessment (CCC, 0.982) than in single-ROI analysis (CCC, 0.756). For both readers, ADC values for clear cell RCC found on single-ROI assessment (2.19 and 2.08 × 10(-3) mm(2)/s) and whole-tumor assessment (2.30 and 2.32 × 10(-3) mm(2)/s) were statistically significantly higher than those for chromophobe, papillary, or unclassified RCC (p < 0.05) but were similar to those for oncocytoma found on single-ROI assessment (2.14 and 2.32 × 10(-3) mm(2)/s) and whole-tumor assessment (2.38 and 2.24 × 10(-3) mm(2)/s). ADC values were also higher for clear cell RCC than for angiomyolipoma, but the difference was statistically significant only in whole-tumor assessment (p < 0.03).

Conclusion: ADC values were statistically significantly higher for clear cell RCC than for chromophobe, papillary, or unclassified RCC subtypes; however, differentiating clear cell RCC from oncocytoma by use of DWI remains especially challenging, because similar ADC values have been shown for these two tumor types.
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http://dx.doi.org/10.2214/AJR.14.13923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826468PMC
January 2016

Updates in advanced diffusion-weighted magnetic resonance imaging techniques in the evaluation of prostate cancer.

World J Radiol 2015 Aug;7(8):184-8

Hebert Alberto Vargas, Edward Malnor Lawrence, Yousef Mazaheri, Evis Sala, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States.

Diffusion-weighted magnetic resonance imaging (DW-MRI) is considered part of the standard imaging protocol for the evaluation of patients with prostate cancer. It has been proven valuable as a functional tool for qualitative and quantitative analysis of prostate cancer beyond anatomical MRI sequences such as T2-weighted imaging. This review discusses ongoing controversies in DW-MRI acquisition, including the optimal number of b-values to be used for prostate DWI, and summarizes the current literature on the use of advanced DW-MRI techniques. These include intravoxel incoherent motion imaging, which better accounts for the non-mono-exponential behavior of the apparent diffusion coefficient as a function of b-value and the influence of perfusion at low b-values. Another technique is diffusion kurtosis imaging (DKI). Metrics from DKI reflect excess kurtosis of tissues, representing its deviation from Gaussian diffusion behavior. Preliminary results suggest that DKI findings may have more value than findings from conventional DW-MRI for the assessment of prostate cancer.
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http://dx.doi.org/10.4329/wjr.v7.i8.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553248PMC
August 2015
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