Intravoxel incoherent motion and diffusion kurtosis imaging and their machine-learning-based texture analysis for detection and assessment of prostate cancer severity at 3 T.

OBJECTIVES: To evaluate the role of combined intravoxel incoherent motion and diffusion kurtosis imaging (IVIM-DKI) and their machine-learning-based texture analysis for the detection and assessment of severity in prostate cancer (PCa). MATERIALS AND METHODS: Eighty-eight patients underwent MRI on a 3 T scanner after giving informed consent. IVIM-DKI data were acquired using 13 b values (0-2000 s/mm2) and analyzed using the IVIM-DKI model with the total variation (TV) method. PCa patients were categorized into two groups: clinically insignificant prostate cancer (CISPCa) (Gleason grade ≤ 6) and clinically significant prostate cancer (CSPCa) (Gleason grade ≥ 7). One-way analysis-of-variance, t test, and receiver operating characteristic analysis was performed to measure the discriminative ability to detect PCa using IVIM-DKI parameters. A chi-square test was used to select important texture features of apparent diffusion coefficient (ADC) and IVIM-DKI parameters. These selected texture features were used in an artificial neural network for PCa detection. RESULTS: ADC and diffusion coefficient (D) were significantly lower (p < 0.001), and kurtosis (k) was significantly higher (p < 0.001), in PCa as compared with benign prostatic hyperplasia (BPH) and normal peripheral zone (PZ). ADC, D, and k showed high areas under the curves (AUCs) of 0.92, 0.89, and 0.88, respectively, in PCa detection. ADC and D were significantly lower (p < 0.05) as compared with CISPCa versus CSPCa. D for detecting CSPCa was high, with an AUC of 0.63. A negative correlation of ADC and D with GS (ADC, ρ = -0.33; D, ρ = -0.35, p < 0.05) and a positive correlation of k with GS (ρ = 0.22, p < 0.05) were observed. Combined IVIM-DKI texture showed high AUC of 0.83 for classification of PCa, BPH, and normal PZ. CONCLUSION: D, f, and k computed using the IVIM-DKI model with the TV method were able to differentiate PCa from BPH and normal PZ. Texture features of combined IVIM-DKI parameters showed high accuracy and AUC in PCa detection.

Radiologists' Rating for Comparative Qualitative Assessment of Intravoxel Incoherent Motion Using Novel Analysis Methods.

OBJECTIVE: The objective was to assess qualitative interpretability and quantitative precision and reproducibility of intravoxel incoherent motion ( IVIM) parametric images evaluated using novel IVIM analysis methods for diagnostic accuracy. METHODS: Intravoxel incoherent motion datasets of 55 patients (male/female = 41:14; age = 17.8 ± 5.5 years) with histopathology-proven osteosarcoma were analyzed. Intravoxel incoherent motion parameters-diffusion coefficient ( D ), perfusion fraction ( f ), and perfusion coefficient ( D* )-were estimated using 5 IVIM analysis methods-(i) biexponential (BE) model, (ii) BE-segmented fitting 2-parameter (BESeg-2), (iii) BE-segmented fitting 1-parameter (BESeg-1), (iv) BE model with total variation penalty function (BE + TV), and (v) BE model with Huber penalty function (BE + HPF). Qualitative scoring in a 5-point Likert scale (uninterpretable: 1; poor: 2; fair: 3; good: 4; excellent: 5) was performed by 2 radiologists for 4 criteria: (a) tumor shape and margin, (b) morphologic correlation, (c) noise suppression, and (d) overall interpretability. Interobserver agreement was evaluated using Spearman rank-order correlation ( rs ). Precision and reproducibility were evaluated using within-subject coefficient of variation (wCV) and between-subject coefficient of variation (bCV). RESULTS: BE + TV and BE + HPF produced significantly ( P < 10 -3 ) higher qualitative scores for D (fair-good [3.3-3.8]) than BE (poor [2.3]) and for D* (poor-fair [2.2-2.7]) and f (fair-good [3.2-3.8]) than BE, BESeg-2, and BESeg-1 ( D* : uninterpretable-poor [1.3-1.9] and f : poor-fair [1.5-3]). Interobserver agreement for qualitative scoring was rs = 0.48-0.59, P < 0.009. BE + TV and BE + HPF showed significantly ( P < 0.05) improved reproducibility in estimating D (wCV: 24%-31%, bCV: 21%-31% improvement) than the BE method and D* (wCV: 4%-19%, bCV: 5%-19% improvement) and f (wCV: 25%-49%, bCV: 25%-47% improvement) than BE, BESeg-2, and BESeg-1 methods. CONCLUSIONS: BE + TV and BE + HPF demonstrated qualitatively and quantitatively improved IVIM parameter estimation and may be considered for clinical use further.

Chemotherapy response evaluation using diffusion weighted MRI in Ewing Sarcoma: A single center experience.

BACKGROUND: Non-invasive biomarkers for early chemotherapeutic response in Ewing sarcoma family of tumors (ESFT) are useful for optimizing existing treatment protocol. PURPOSE: To assess the role of diffusion-weighted magnetic resonance imaging (MRI) in the early evaluation of chemotherapeutic response in ESFT. MATERIAL AND METHODS: A total of 28 patients (mean age = 17.2 ± 5.6 years) with biopsy proven ESFT were analyzed prospectively. Patients underwent MRI acquisition on a 1.5-T scanner at three time points: before starting neoadjuvant chemotherapy (baseline), after first cycle chemotherapy (early time point), and after completion of chemotherapy (last time point). RECIST 1.1 criteria was used to evaluate the response to chemotherapy and patients were categorized as responders (complete and partial response) and non-responders (stable and progressive disease). Tumor diameter, absolute apparent diffusion coefficient (ADC), and normalized ADC (nADC) values in the tumor were measured. Baseline parameters and relative percentage change of parameters after first cycle chemotherapy were assessed for early detection of chemotherapy response. RESULTS: The responder:non-responder ratio was 21:7. At baseline, ADC ([0.864 ± 0.266 vs. 0.977 ± 0.246]) × 10-3mm2/s; P = 0.205) and nADC ([0.740 ± 0.254 vs. 0.925 ± 0.262] × 10-3mm2/s; P = 0.033) among responders was lower than the non-responders and predicted response to chemotherapy with AUCs of 0.6 and 0.735, respectively. At the early time point, tumor diameter (27% ± 14% vs. 4.6% ± 10%; P = 0.002) showed a higher reduction and ADC (75% ± 44% vs. 52% ± 72%; P = 0.039) and nADC (81% ± 44% vs. 48% ± 67%; P = 0.008) showed a higher increase in mean values among responders than the non-responders and identified chemotherapy response with AUC of 0.890, 0.723, and 0.756, respectively. CONCLUSION: Baseline nADC and its change after the first cycle of chemotherapy can be used as non-invasive surrogate markers of early chemotherapeutic response in patients with ESFT.

Non-invasive intravoxel incoherent motion MRI in prediction of histopathological response to neoadjuvant chemotherapy and survival outcome in osteosarcoma at the time of diagnosis.

BACKGROUND: Early prediction of response to neoadjuvant chemotherapy (NACT) is important to aid personalized treatment in osteosarcoma. Diffusion-weighted Intravoxel Incoherent Motion (IVIM) MRI was used to evaluate the predictive value for response to NACT and survival outcome in osteosarcoma. METHODS: Total fifty-five patients with biopsy-proven osteosarcoma were recruited prospectively, among them 35 patients were further analysed. Patients underwent 3 cycles of NACT (Cisplatin + Doxorubicin) followed by surgery and response adapted adjuvant chemotherapy. Treatment outcomes were histopathological response to NACT (good-response ≥ 50% necrosis and poor-response < 50% necrosis) and survival outcome (event-free survival (EFS) and overall survival (OS)). IVIM MRI was acquired at 1.5T at baseline (t0), after 1-cycle (t1) and after 3-cycles (t2) of NACT. Quantitative IVIM parameters (D, D*, f & D*.f) were estimated using advanced state-of-the-art spatial penalty based IVIM analysis method bi-exponential model with total-variation penalty function (BETV) at 3 time-points and histogram analysis was performed. RESULTS: Good-responders: Poor-responders ratio was 13 (37%):22 (63%). EFS and OS were 31% and 69% with 16.27 and 25.9 months of median duration respectively. For predicting poor-response to NACT, IVIM parameters showed AUC = 0.87, Sensitivity = 86%, Specificity = 77% at t0, and AUC = 0.96, Sensitivity = 86%, Specificity = 100% at t1. Multivariate Cox regression analysis showed smaller tumour volume (HR = 1.002, p = 0.001) higher ADC-25th-percentile (HR = 0.047, p = 0.005) & D-Mean (HR = 0.1, p = 0.023) and lower D*-Mean (HR = 1.052, p = 0.039) were independent predictors of longer EFS (log-rank p-values: 0.054, 0.0034, 0.0017, 0.0019 respectively) and non-metastatic disease (HR = 4.33, p < 10-3), smaller tumour-volume (HR = 1.001, p = 0.042), lower D*-Mean (HR = 1.045, p = 0.056) and higher D*.f-skewness (HR = 0.544, p = 0.048) were independent predictors of longer OS (log-rank p-values: < 10-3, 0.07, < 10-3, 0.019 respectively). CONCLUSION: IVIM parameters obtained with a 1.5T scanner along with novel BETV method and their histogram analysis indicating tumour heterogeneity were informative in characterizing NACT response and survival outcome in osteosarcoma.

Device for Assessing Knee Joint Dynamics During Magnetic Resonance Imaging.

BACKGROUND: Knee assessment with and without load using magnetic resonance imaging (MRI) can provide information on knee joint dynamics and improve the diagnosis of knee joint diseases. Performing such studies on a routine MRI-scanner require a load-exerting device during scanning. There is a need for more studies on developing loading devices and evaluating their clinical potential. PURPOSE: Design and develop a portable and easy-to-use axial loading device to evaluate the knee joint dynamics during the MRI study. STUDY TYPE: Prospective study. SUBJECTS: Nine healthy subjects. FIELD STRENGTH/SEQUENCE: A 0.25 T standing-open MRI and 3.0 T MRI. PD-T2 -weighted FSE, 3D-fast-spoiled-gradient-echo, FS-PD, and CartiGram sequences. ASSESSMENT: Design and development of loading device, calibration of loads, MR safety assessment (using projectile angular displacement, torque, and temperature tests). Scoring system for ease of doing. Qualitative (by radiologist) and quantitative (using structural similarity index measure [SSIM]) image-artifact assessment. Evaluation of repeatability, comparison with various standing stances load, and loading effect on knee MR parameters (tibiofemoral bone gap [TFBG], femoral cartilage thickness [FCT], tibial cartilage thickness [TCT], femoral cartilage T2 -value [FCT2], and tibia cartilage T2 -value [TCT2]). The relative percentage change (RPC) in parameters due to the device load was computed. STATISTICAL TEST: Pearson's correlation coefficient (r). RESULTS: The developed device is conditional-MR safe (details in the manuscript and supplementary materials), 15 × 15 × 45 cm3 dimension, and <3 kg. The ease of using the device was 4.9/5. The device introduced no visible image artifacts, and SSIM of 0.9889 ± 0.0153 was observed. The TFBG intraobserver variability (absolute difference) was <0.1 mm. Interobserver variability of all regions of interest was <0.1 mm. The load exerted by the device was close to the load during standing on both legs in 0.25 T scanner with r > 0.9. Loading resulted in RPC of 1.5%-11.0%, 7.9%-8.5%, and -1.5% to 13.0% in the TFBG, FCT, and TCT, respectively. FCT2 and TCT2 were reduced in range of 1.5-2.7 msec and 0.5-2.3 msec due to load. DATA CONCLUSION: The proposed device is conditionally MR safe, low cost (material cost < INR 6000), portable, and effective in loading the knee joint with up to 50% of body weight. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

IVIM-DKI for differentiation between prostate cancer and benign prostatic hyperplasia: comparison of 1.5 T vs. 3 T MRI.

OBJECTIVE: To implement an advanced spatial penalty-based reconstruction to constrain the intravoxel incoherent motion (IVIM)-diffusion kurtosis imaging (DKI) model and investigate whether it provides a suitable alternative at 1.5 T to the traditional IVIM-DKI model at 3 T for clinical characterization of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Thirty-two patients with biopsy-proven PCa were recruited for MRI examination (n = 16 scanned at 1.5 T, n = 16 scanned at 3 T). Diffusion-weighted imaging (DWI) with 13 b values (b = 0 to 2000 s/mm2 up to 3 averages, 1.5 T: TR = 5.774 s, TE = 81 ms and 3 T: TR = 4.899 s, TE = 100 ms), T2-weighted, and T1-weighted imaging were used on the 1.5 T and 3 T MRI scanner, respectively. The IVIM-DKI signal was modeled using the traditional IVIM-DKI model and a novel model in which the total variation (TV) penalty function was combined with the traditional model to optimize non-physiological variations. Paired and unpaired t-tests were used to compare intra-scanner and scanner group differences in IVIM-DKI parameters obtained using the novel and the traditional models. Analysis of variance with post hoc test and receiver operating characteristic (ROC) curve analysis were used to assess the ability of parameters obtained using the novel model (at 1.5 T) and the traditional model (at 3 T) to characterize prostate lesions. RESULTS: IVIM-DKI modeled using novel model with TV spatial penalty function at 1.5 T, produced parameter maps with 50-78% lower coefficient of variation (CV) than traditional model at 3 T. Novel model estimated higher D with lower D*, f and k values at both field strengths compared to traditional model. For scanner differences, the novel model at 1.5 T estimated lower D* and f values as compared to traditional model at 3 T. At 1.5 T, D and f values were significantly lower with k values significantly higher in tumor than BPH and healthy tissue. D (AUC: 0.98), f (AUC: 0.82), and k (AUC: 0.91) parameters estimated using novel model showed high diagnostic performance in cancer lesion detection at 1.5 T. DISCUSSION: In comparison with the IVIM-DKI model at 3 T, IVIM-DKI signal modeled with the TV penalty function at 1.5 T showed lower estimation errors. The proposed novel model can be utilized for improved detection of prostate lesions.

Machine learning based reanalysis of clinical scores for distinguishing between ischemic and hemorrhagic stroke in low resource setting.

BACKGROUND: Identifying ischemic or hemorrhagic strokes clinically may help in situations where neuroimaging is unavailable to provide primary-care prior to referring to stroke-ready facility. Stroke classification-based solely on clinical scores faces two unresolved issues. One pertains to overestimation of score performance, while other is biased performance due to class-imbalance inherent in stroke datasets. After correcting the issues using Machine Learning theory, we quantitatively compared existing scores to study the capabilities of clinical attributes for stroke classification. METHODS: We systematically searched PubMed, ERIC, ScienceDirect, and IEEE-Xplore from 2001 to 2021 for studies that validated the Siriraj, Guys Hospital/Allen, Greek, and Besson scores for stroke classification. From included studies we extracted the reported cross-tabulation to identify and correct the above listed issues for an accurate comparative analysis of the performance of clinical scores. RESULTS: A total of 21 studies were included. Comparative analysis demonstrates Siriraj Score outperforms others. For Siriraj Score the reported sensitivity range (Ischemic Stroke-diagnosis) 43-97% (Median = 78% [IQR 65-88%]) is significantly higher than our calculated range 40-90% (Median = 70% [IQR 57-73%]), also the reported sensitivity range (Hemorrhagic Stroke-diagnosis) 50-95% (Median = 71% [IQR 64-82%]) is higher than our calculated range 34-86% (Median = 59% [IQR 50-79%]) which indicates overestimation of performance by the included studies. Guys Hospital/Allen and Greek Scores show similar trends. Recommended weighted-accuracy metric provides better estimate of the performance. CONCLUSION: We demonstrate that clinical attributes have a potential for stroke classification, however the performance of all scores varies across demographics, indicating the need to fine-tune scores for different demographics. To improve this variability, we suggest creating global data pool with statistically significant attributes. Machine Learning classifiers trained over such dataset may perform better and generalise at scale.

Model for in-vivo estimation of stiffness of tibiofemoral joint using MR imaging and FEM analysis.

BACKGROUND: Appropriate structural and material properties are essential for finite-element-modeling (FEM). In knee FEM, structural information could extract through 3D-imaging, but the individual subject's tissue material properties are inaccessible. PURPOSE: The current study's purpose was to develop a methodology to estimate the subject-specific stiffness of the tibiofemoral joint using finite-element-analysis (FEA) and MRI data of knee joint with and without load. METHODS: In this study, six Magnetic Resonance Imaging (MRI) datasets were acquired from 3 healthy volunteers with axially loaded and unloaded knee joint. The strain was computed from the tibiofemoral bone gap difference (ΔmBGFT) using the knee MR images with and without load. The knee FEM study was conducted using a subject-specific knee joint 3D-model and various soft-tissue stiffness values (1 to 50 MPa) to develop subject-specific stiffness versus strain models. RESULTS: Less than 1.02% absolute convergence error was observed during the simulation. Subject-specific combined stiffness of weight-bearing tibiofemoral soft-tissue was estimated with mean values as 2.40 ± 0.17 MPa. Intra-subject variability has been observed during the repeat scan in 3 subjects as 0.27, 0.12, and 0.15 MPa, respectively. All subject-specific stiffness-strain relationship data was fitted well with power function (R2 = 0.997). CONCLUSION: The current study proposed a generalized mathematical model and a methodology to estimate subject-specific stiffness of the tibiofemoral joint for FEM analysis. Such a method might enhance the efficacy of FEM in implant design optimization and biomechanics for subject-specific studies. Trial registration The institutional ethics committee (IEC), Indian Institute of Technology, Delhi, India, approved the study on 20th September 2017, with reference number P-019; it was a pilot study, no clinical trail registration was recommended.

Characterisation of prostate cancer using texture analysis for diagnostic and prognostic monitoring.

Automated classification of significant prostate cancer (PCa) using MRI plays a potential role in assisting in clinical decision-making. Multiparametric MRI using a machine-aided approach is a better step to improve the overall accuracy of diagnosis of PCa. The objective of this study was to develop and validate a framework for differentiating Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) grades (grade 2 to grade 5) of PCa using texture features and machine learning (ML) methods with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC). The study cohort included an MRI dataset of 59 patients with clinically proven PCa. Regions of interest (ROIs) for a total of 435 lesions were delineated from the segmented peripheral zones of DWI and ADC. Six texture methods comprising 98 texture features in total (49 each of DWI and ADC) were extracted from lesion ROIs. Random forest (RF) and correlation-based feature selection methods were applied on feature vectors to select the best features for classification. Two ML classifiers, support vector machine (SVM) and K-nearest neighbour, were used and validated by 10-fold cross-validation. The proposed framework achieved high diagnostic performance with a sensitivity of 85.25% ± 3.84%, specificity of 95.71% ± 1.96%, accuracy of 84.90% ± 3.37% and area under the receiver-operating characteristic curve of 0.98 for PI-RADS v2 grades (2 to 5) classification using the RF feature selection method and Gaussian SVM classifier with combined features of DWI + ADC. The proposed computer-assisted framework can distinguish between PCa lesions with different aggressiveness based on PI-RADS v2 standards using texture analysis to improve the efficiency of PCa diagnostic performance.

Texture analysis for chemotherapy response evaluation in osteosarcoma using MR imaging.

The efficacy of MRI-based statistical texture analysis (TA) in predicting chemotherapy response among patients with osteosarcoma was assessed. Forty patients (male: female = 31:9; age = 17.2 ± 5.7 years) with biopsy-proven osteosarcoma were analyzed in this prospective study. Patients were scheduled for three cycles of neoadjuvant chemotherapy (NACT) and diffusion-weighted MRI acquisition at three time points: at baseline (t0), after the first NACT (t1) and after the third NACT (t2) using a 1.5 T scanner. Eight patients (nonsurvivors) died during NACT while 34 patients (survivors) completed the NACT regimen followed by surgery. Histopathological evaluation was performed in the resected tumor to assess NACT response (responder [≤50% viable tumor] and nonresponder [>50% viable tumor]) and revealed nonresponder: responder = 20:12. Apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) parameters, diffusion coefficient (D), perfusion coefficient (D*) and perfusion fraction (f) were evaluated. A total of 25 textural features were evaluated on ADC, D, D* and f parametric maps and structural T1-weighted (T1W) and T2-weighted (T2W) images in the entire tumor volume using 3D TA methods gray-level cooccurrence matrix (GLCM), neighborhood gray-tone-difference matrix (NGTDM) and run-length matrix (RLM). Receiver-operating-characteristic curve analysis was performed on the selected textural feature set to assess the role of TA features (a) as marker(s) of tumor aggressiveness leading to mortality at baseline and (b) in predicting the NACT response among survivors in the course of treatment. Findings showed that the NGTDM features coarseness, busyness and strength quantifying tumor heterogeneity in D, D* and f maps and T1W and T2W images were useful markers of tumor aggressiveness in identifying the nonsurvivor group (area-under-the-curve [AUC] = 0.82-0.88) at baseline. The GLCM features contrast and correlation, NGTDM features contrast and complexity and RLM feature short-run-low-gray-level-emphasis quantifying homogeneity/terogeneity in tumor were effective markers for predicting chemotherapeutic response using D (AUC = 0.80), D* (AUC = 0.80) and T2W (AUC = 0.70) at t0, and D* (AUC = 0.80) and f (AUC = 0.70) at t1. 3D statistical TA features might be useful as imaging-based markers for characterizing tumor aggressiveness and predicting chemotherapeutic response in patients with osteosarcoma.