Assessment of Hypoxia in Breast Cancer: Emerging Functional MR Imaging and Spectroscopy Techniques and Clinical Applications.

Breast cancer is one of the most prevalent forms of cancer affecting women worldwide. Hypoxia, a condition characterized by insufficient oxygen supply in tumor tissues, is closely associated with tumor aggressiveness, resistance to therapy, and poor clinical outcomes. Accurate assessment of tumor hypoxia can guide treatment decisions, predict therapy response, and contribute to the development of targeted therapeutic interventions. Over the years, functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) techniques have emerged as promising noninvasive imaging options for evaluating hypoxia in cancer. Such techniques include blood oxygen level-dependent (BOLD) MRI, oxygen-enhanced MRI (OE) MRI, chemical exchange saturation transfer (CEST) MRI, and proton MRS (1H-MRS). These may help overcome the limitations of the routinely used dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) techniques, contributing to better diagnosis and understanding of the biological features of breast cancer. This review aims to provide a comprehensive overview of the emerging functional MRI and MRS techniques for assessing hypoxia in breast cancer, along with their evolving clinical applications. The integration of these techniques in clinical practice holds promising implications for breast cancer management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Bioresource Polymer Composite for Energy Generation and Storage: Developments and Trends.

The ever-growing demand of human society for clean and reliable energy sources spurred a substantial academic interest in exploring the potential of biological resources for developing energy generation and storage systems. As a result, alternative energy sources are needed in populous developing countries to compensate for energy deficits in an environmentally sustainable manner. This review aims to evaluate and summarize the recent progress in bio-based polymer composites (PCs) for energy generation and storage. The articulated review provides an overview of energy storage systems, e. g., supercapacitors and batteries, and discusses the future possibilities of various solar cells (SCs), using both past research progress and possible future developments as a basis for discussion. These studies examine systematic and sequential advances in different generations of SCs. Developing novel PCs that are efficient, stable, and cost-effective is of utmost importance. In addition, the current state of high-performance equipment for each of the technologies is evaluated in detail. We also discuss the prospects, future trends, and opportunities regarding using bioresources for energy generation and storage, as well as the development of low-cost and efficient PCs for SCs.

Convolutional network denoising for acceleration of multi-shot diffusion MRI.

Multi-shot echo planar imaging is a promising technique to reduce geometric distortions and increase spatial resolution in diffusion-weighted MRI (DWI), at the expense of increased scan time. Moreover, performing DWI in the body requires multiple repetitions to obtain sufficient signal-to-noise ratio, which further increases the scan time. This work proposes to reduce the number of repetitions and perform denoising of high b-value images using a convolutional network denoising trained on single-shot DWI to accelerate the acquisition of multi-shot DWI. Convolutional network denoising is demonstrated to accelerate the acquisition of 2-shot DWI by a factor of 4 compared to the clinical standard on patients with rectal cancer. Image quality was evaluated using qualitative scores from expert body radiologists between accelerated and non-accelerated acquisition. Additionally, the effect of convolutional network denoising on each image quality score was analyzed using a Wilcoxon signed-rank test. Convolutional network denoising would enable to increase the number of shots without increasing scan time for significant geometric artifact reduction and spatial resolution increase.

Human prostate MRI at ultrahigh-performance gradient: A feasibility study.

PURPOSE: To demonstrate the technical feasibility and the value of ultrahigh-performance gradient in imaging the prostate in a 3T MRI system. METHODS: In this local institutional review board-approved study, prostate MRI was performed on 4 healthy men. Each subject was scanned in a prototype 3T MRI system with a 42-cm inner-diameter gradient coil that achieves a maximum gradient amplitude of 200 mT/m and slew rate of 500 T/m/s. PI-RADS V2.1-compliant axial T2 -weighted anatomical imaging and single-shot echo planar DWI at standard gradient of 70 mT/m and 150 T/m/s were obtained, followed by DWI at maximum performance (i.e., 200 mT/m and 500 T/m/s). In comparison to state-of-the-art clinical whole-body MRI systems, the high slew rate improved echo spacing from 1020 to 596 µs and, together with a high gradient amplitude for diffusion encoding, TE was reduced from 55 to 36 ms. RESULTS: In all 4 subjects (waist circumference = 81-91 cm, age = 45-65 years), no peripheral nerve stimulation sensation was reported during DWI. Reduced image distortion in the posterior peripheral zone prostate gland and higher signal intensity, such as in the surrounding muscle of high-gradient DWI, were noted. CONCLUSION: Human prostate MRI at simultaneously high gradient amplitude of 200 mT/m and slew rate of 500 T/m/s is feasible, demonstrating that improved gradient performance can address image distortion and T2 decay-induced SNR issues for in vivo prostate imaging.

Multiplexed sensitivity-encoding diffusion-weighted imaging (MUSE) in diffusion-weighted imaging for rectal MRI: a quantitative and qualitative analysis at multiple b-values.

PURPOSE: To compare four diffusion-weighted imaging (DWI) sequences for image quality, rectal contour, and lesion conspicuity, and to assess the difference in their signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC). METHODS: In this retrospective study of 36 consecutive patients who underwent 3.0 T rectal MRI from January-June 2020, DWI was performed with single-shot echo planar imaging (ss-EPI) (b800 s/mm2), multiplexed sensitivity encoding (MUSE) (b800 s/mm2), MUSE (b1500 s/mm2), and field-of-view optimized and constrained undistorted single-shot (FOCUS) (b1500 s/mm2). Two radiologists independently scored image quality using a 5-point Likert scale. Inter-reader agreement was assessed using the weighted Cohen's к. SNR, CNR, and ADC measurements were compared using the paired t-test. RESULTS: For both readers, MUSE b800 scored significantly higher for image quality, rectal contour, and lesion conspicuity compared to ss-EPI; MUSE b800 also scored significantly higher for image quality and rectal contour compared to all other sequences. Lesion conspicuity was equally superior for MUSE b800 and MUSE b1500 compared to the other two sequences. There was good to excellent inter-reader agreement for all qualitative features (к = 0.72-0.88). MUSE b800 had the highest SNR; MUSE b1500 had the highest CNR. A significant difference in ADC was observed between ss-EPI compared to the other sequences (p < 0.001) and between MUSE b800 and FOCUS. No significant difference in ADC was found between MUSE b1500 and FOCUS b1500. CONCLUSION: MUSE b800 improved image quality over ss-EPI and both MUSE b800 and b1500 showed better tumor conspicuity compared to conventional ss-EPI.

Rectal MRI Interpretation After Neoadjuvant Therapy.

In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

Evaluation of cancer outcome assessment using MRI: A review of deep-learning methods.

Accurate evaluation of tumor response to treatment is critical to allow personalized treatment regimens according to the predicted response and to support clinical trials investigating new therapeutic agents by providing them with an accurate response indicator. Recent advances in medical imaging, computer hardware, and machine-learning algorithms have resulted in the increased use of these tools in the field of medicine as a whole and specifically in cancer imaging for detection and characterization of malignant lesions, prognosis, and assessment of treatment response. Among the currently available imaging techniques, magnetic resonance imaging (MRI) plays an important role in the evaluation of treatment assessment of many cancers, given its superior soft-tissue contrast and its ability to allow multiplanar imaging and functional evaluation. In recent years, deep learning (DL) has become an active area of research, paving the way for computer-assisted clinical and radiological decision support. DL can uncover associations between imaging features that cannot be visually identified by the naked eye and pertinent clinical outcomes. The aim of this review is to highlight the use of DL in the evaluation of tumor response assessed on MRI. In this review, we will first provide an overview of common DL architectures used in medical imaging research in general. Then, we will review the studies to date that have applied DL to magnetic resonance imaging for the task of treatment response assessment. Finally, we will discuss the challenges and opportunities of using DL within the clinical workflow.

Phase II Study of Neoadjuvant Nivolumab in Patients with Locally Advanced Clear Cell Renal Cell Carcinoma Undergoing Nephrectomy.

Immune checkpoint inhibitor therapy improves survival in patients with metastatic renal cell carcinoma (RCC) but has not been studied well preoperatively in patients with localized disease undergoing nephrectomy. We conducted a single-center study to evaluate the safety and feasibility of neoadjuvant nivolumab in patients undergoing nephrectomy for localized RCC. Eligible patients had a >20% risk of recurrence, as estimated by a preoperative nomogram. Patients received nivolumab every 2 wk for four treatments prior to surgery. The primary endpoints were feasibility, defined as completing at least three treatments without significant surgical delay, and safety, defined as the rate of surgical complications. Treatment effects were assessed by radiomics and immunohistochemistry. A total of 18 patients (11 men; median age 60 yr) with clear cell RCC were enrolled. All received at least one dose of nivolumab and proceeded to nephrectomy without delay; 16/18 patients completed all four doses. Two patients discontinued nivolumab for immune-related adverse events, and four had surgical complications as per the Clavien-Dindo classification. Integrated pathology plus radiomic analysis demonstrated an association between post-treatment immune infiltration and low entropy apparent diffusion coefficient on magnetic resonance imaging. Nivolumab prior to nephrectomy was safe and feasible, without significant surgical delays and with an expected rate of immune-related adverse events. PATIENT SUMMARY: We evaluated the outcomes for patients with localized kidney cancer who received immunotherapy prior to surgery to remove their kidney tumor. In a small group of patients who had cancer confined to the kidney, this approach appeared safe and feasible.

Dynamic contrast-enhanced MRI parametric mapping using high spatiotemporal resolution Golden-angle RAdial Sparse Parallel MRI and iterative joint estimation of the arterial input function and pharmacokinetic parameters.

The aim of this work is to develop a data-driven quantitative dynamic contrast-enhanced (DCE) MRI technique using Golden-angle RAdial Sparse Parallel (GRASP) MRI with high spatial resolution and high flexible temporal resolution and pharmacokinetic (PK) analysis with an arterial input function (AIF) estimated directly from the data obtained from each patient. DCE-MRI was performed on 13 patients with gynecological malignancy using a 3-T MRI scanner with a single continuous golden-angle stack-of-stars acquisition and image reconstruction with two temporal resolutions, by exploiting a unique feature in GRASP that reconstructs acquired data with user-defined temporal resolution. Joint estimation of the AIF (both AIF shape and delay) and PK parameters was performed with an iterative algorithm that alternates between AIF and PK estimation. Computer simulations were performed to determine the accuracy (expressed as percentage error [PE]) and precision of the estimated parameters. PK parameters (volume transfer constant [Ktrans ], fractional volume of the extravascular extracellular space [ve ], and blood plasma volume fraction [vp ]) and normalized root-mean-square error [nRMSE] (%) of the fitting errors for the tumor contrast kinetic data were measured both with population-averaged and data-driven AIFs. On patient data, the Wilcoxon signed-rank test was performed to compare nRMSE. Simulations demonstrated that GRASP image reconstruction with a temporal resolution of 1 s/frame for AIF estimation and 5 s/frame for PK analysis resulted in an absolute PE of less than 5% in the estimation of Ktrans and ve , and less than 11% in the estimation of vp . The nRMSE (mean ± SD) for the dual temporal resolution image reconstruction and data-driven AIF was 0.16 ± 0.04 compared with 0.27 ± 0.10 (p < 0.001) with 1 s/frame using population-averaged AIF, and 0.23 ± 0.07 with 5 s/frame using population-averaged AIF (p < 0.001). We conclude that DCE-MRI data acquired and reconstructed with the GRASP technique at dual temporal resolution can successfully be applied to jointly estimate the AIF and PK parameters from a single acquisition resulting in data-driven AIFs and voxelwise PK parametric maps.

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

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.

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

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.

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

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 IDH 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 IDH mutations in gliomas. This has opened up targeted drug development to inhibit the mutant IDH pathway. This review provides guidance on MRSI in brain gliomas, including its acquisition, analysis methods, and evolving clinical applications.

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

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 b-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 b-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) (P < .001 for all). Compared with the reference images, the denoised images received higher image quality scores from the readers (P < .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 × 10-3 mm2/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. Supplemental material is available for this article. © RSNA, 2020.

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

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 Ktrans values (min-1, 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 × (10-7 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, P = 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.

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

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/mm2 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 (P > .05). We observed improvement in spatial accuracy for MUSE-DWEPI with RPG in the head and neck region with a higher correlation (R2 = 0.791) compared with that for SS-DWEPI (R2 = 0.707) and MUSE-DWEPI (R2 = 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.

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

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.

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

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.

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

The purpose of this study was to identify the optimal tracer kinetic model from T1 -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 Ktrans 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-1 , P = 0.005). From ROC analysis, cut-off values of Ktrans , ve and vp , which discriminated between PTCs with and without ETE, were determined at 0.45 min-1 , 0.28 and 0.014 respectively. The sensitivities and specificities were 86 and 82% (Ktrans ), 71 and 82% (ve ), and 86 and 55% (vp ), respectively. Their respective AUCs were 0.90, 0.71 and 0.71. We conclude that ETM Ktrans has shown potential to classify tumors with and without aggressive ETE in patients with PTC.

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

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/s2) 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 (Dsum) 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 Dsum 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 Dsum 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%.