Radiomic signatures from T2W and DWI MRI are predictive of tumour hypoxia in colorectal liver metastases.

BACKGROUND: Tumour hypoxia is a negative predictive and prognostic biomarker in colorectal cancer typically assessed by invasive sampling methods, which suffer from many shortcomings. This retrospective proof-of-principle study explores the potential of MRI-derived imaging markers in predicting tumour hypoxia non-invasively in patients with colorectal liver metastases (CLM). METHODS: A single-centre cohort of 146 CLMs from 112 patients were segmented on preoperative T2-weighted (T2W) images and diffusion-weighted imaging (DWI). HIF-1 alpha immunohistochemical staining index (high/low) was used as a reference standard. Radiomic features were extracted, and machine learning approaches were implemented to predict the degree of histopathological tumour hypoxia. RESULTS: Radiomic signatures from DWI b200 (AUC = 0.79, 95% CI 0.61-0.93, p = 0.002) and ADC (AUC = 0.72, 95% CI 0.50-0.90, p = 0.019) were significantly predictive of tumour hypoxia. Morphological T2W TE75 (AUC = 0.64, 95% CI 0.42-0.82, p = 0.092) and functional DWI b0 (AUC = 0.66, 95% CI 0.46-0.84, p = 0.069) and b800 (AUC = 0.64, 95% CI 0.44-0.82, p = 0.071) images also provided predictive information. T2W TE300 (AUC = 0.57, 95% CI 0.33-0.78, p = 0.312) and b = 10 (AUC = 0.53, 95% CI 0.33-0.74, p = 0.415) images were not predictive of tumour hypoxia. CONCLUSIONS: T2W and DWI sequences encode information predictive of tumour hypoxia. Prospective multicentre studies could help develop and validate robust non-invasive hypoxia-detection algorithms. CRITICAL RELEVANCE STATEMENT: Hypoxia is a negative prognostic biomarker in colorectal cancer. Hypoxia is usually assessed by invasive sampling methods. This proof-of-principle retrospective study explores the role of AI-based MRI-derived imaging biomarkers in non-invasively predicting tumour hypoxia in patients with colorectal liver metastases (CLM).

Breast DWI Analyzed Before and After Gadolinium Contrast Administration-An Intrapatient Analysis on 1.5 T and 3.0 T.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging (MRI) is gaining popularity as an addition to standard dynamic contrast-enhanced breast MRI. Although adding diffusion-weighted imaging (DWI) to the standard protocol design would require increased scanning-time, implementation during the contrast-enhanced phase could offer a multiparametric MRI protocol without any additional scanning time. However, gadolinium within a region of interest (ROI) might affect assessments of DWI. This study aims to determine if acquiring DWI postcontrast, incorporated in an abbreviated MRI protocol, would statistically significantly affect lesion classification. In addition, the effect of postcontrast DWI on breast parenchyma was studied. MATERIALS AND METHODS: Screening or preoperative MRIs (1.5 T/3 T) were included for this study. Diffusion-weighted imaging was acquired with single-shot spin echo-echo planar imaging before and at approximately 2 minutes after gadoterate meglumine injection. Apparent diffusion coefficients (ADCs) based on 2-dimensional ROIs of fibroglandular tissue, as well as benign and malignant lesions at 1.5 T/3.0 T, were compared with a Wilcoxon signed rank test. Diffusivity levels were compared between precontrast and postcontrast DWI with weighted κ. An overall P ≤ 0.05 was considered statistically significant. RESULTS: No significant changes were observed in ADC mean after contrast administration in 21 patients with 37 ROI of healthy fibroglandular tissue and in the 93 patients with 93 (malignant and benign) lesions. This effect remained after stratification on B 0 . In 18% of all lesions, a diffusion level shift was observed, with an overall weighted κ of 0.75. CONCLUSIONS: This study supports incorporating DWI at 2 minutes postcontrast when ADC is calculated based on b150-b800 with 15 mL 0.5 M gadoterate meglumine in an abbreviated multiparametric MRI protocol without requiring extra scan time.

Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis.

An increasing number of breast cancer patients develop brain metastases (BM). Standard-of-care treatments are largely inefficient, and breast cancer brain metastasis (BCBM) patients are considered untreatable. Immunotherapies are not successfully employed in BCBM, in part because breast cancer is a "cold" tumor and also because the brain tissue has a unique immune landscape. Here, we generate and characterize immunocompetent models of BCBM derived from PyMT and Neu mammary tumors to test how harnessing the pro-senescence properties of doxorubicin can be used to prime the specific immune BCBM microenvironment. We reveal that BCBM senescent cells, induced by doxorubicin, trigger the recruitment of PD1-expressing T cells to the brain. Importantly, we demonstrate that induction of senescence with doxorubicin improves the efficacy of immunotherapy with anti-PD1 in BCBM in a CD8 T cell-dependent manner, thereby providing an optimized strategy to introduce immune-based treatments in this lethal disease. In addition, our BCBM models can be used for pre-clinical testing of other therapeutic strategies in the future.

T1ρ for Radiotherapy Treatment Response Monitoring in Rectal Cancer Patients: A Pilot Study.

Quantitative MRI has the potential to produce imaging biomarkers for the prediction of early response to radiotherapy treatment. In this pilot study, a potential imaging biomarker, the T1ρ relaxation time, is assessed for this purpose. A T1ρ sequence was implemented on a 1.5 T MR-linac system, a system that combines an MRI with a linear accelerator for radiation treatment. An agar phantom with concentrations of 1-4% w/w was constructed for technical validation of the sequence. Phantom images were assessed in terms of short-term repeatability and signal-to-noise ratio. Twelve rectal cancer patients, who were treated with 5 × 5 Gy, were imaged on each treatment fraction. Individual changes in the T1ρ values of the gross tumor volume (GTV) showed an increase for most patients, although a paired t-test comparing values in the GTV from the first to the last treatment fraction showed no statistically significant difference. The phantom measurements showed excellent short-term repeatability (0.5-1.5 ms), and phantom T1ρ values corresponded to the literature values. T1ρ imaging was implemented successfully on the MR-linac, with a repeatability comparable to diagnostic systems, although clinical benefit in terms of treatment response monitoring remains to be demonstrated.

Factors affecting the value of diffusion-weighted imaging for identifying breast cancer patients with pathological complete response on neoadjuvant systemic therapy: a systematic review.

This review aims to identify factors causing heterogeneity in breast DWI-MRI and their impact on its value for identifying breast cancer patients with pathological complete response (pCR) on neoadjuvant systemic therapy (NST). A search was performed on PubMed until April 2020 for studies analyzing DWI for identifying breast cancer patients with pCR on NST. Technical and clinical study aspects were extracted and assessed for variability. Twenty studies representing 1455 patients/lesions were included. The studies differed with respect to study population, treatment type, DWI acquisition technique, post-processing (e.g., mono-exponential/intravoxel incoherent motion/stretched exponential modeling), and timing of follow-up studies. For the acquisition and generation of ADC-maps, various b-value combinations were used. Approaches for drawing regions of interest on longitudinal MRIs were highly variable. Biological variability due to various molecular subtypes was usually not taken into account. Moreover, definitions of pCR varied. The individual areas under the curve for the studies range from 0.50 to 0.92. However, overlapping ranges of mean/median ADC-values at pre- and/or during and/or post-NST were found for the pCR and non-pCR groups between studies. The technical, clinical, and epidemiological heterogeneity may be causal for the observed variability in the ability of DWI to predict pCR accurately. This makes implementation of DWI for pCR prediction and evaluation based on one absolute ADC threshold for all breast cancer types undesirable. Multidisciplinary consensus and appropriate clinical study design, taking biological and therapeutic variation into account, is required for obtaining standardized, reliable, and reproducible DWI measurements for pCR/non-pCR identification.

Clinical response assessment on DW-MRI compared with FDG-PET/CT after neoadjuvant chemoradiotherapy in patients with oesophageal cancer.

PURPOSE: In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT. METHODS: Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+). RESULTS: Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively. CONCLUSION: MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.

A workflow for automated segmentation of the liver surface, hepatic vasculature and biliary tree anatomy from multiphase MR images.

Accurate assessment of 3D models of patient-specific anatomy of the liver, including underlying hepatic and biliary tree, is critical for preparation and safe execution of complex liver resections, especially due to high variability of biliary and hepatic artery anatomies. Dynamic MRI with hepatospecific contrast agents is currently the only type of diagnostic imaging that provides all anatomical information required for generation of such a model, yet there is no information in the literature on how the complete 3D model can be generated automatically. In this work, a new automated segmentation workflow for extraction of patient-specific 3D model of the liver, hepatovascular and biliary anatomy from a single multiphase MRI acquisition is developed and quantitatively evaluated. The workflow incorporates course 4D k-means clustering estimation and geodesic active contour refinement of the liver boundary, based on organ's characteristic uptake of gadolinium contrast agents overtime. Subsequently, hepatic vasculature and biliary ducts segmentations are performed using multiscale vesselness filters. The algorithm was evaluated using 15 test datasets of patients with liver malignancies of various histopathological types. It showed good correlation with expert manual segmentation, resulting in an average of 1.76 ± 2.44 mm Hausdorff distance for the liver boundary, and 0.58 ± 0.72 and 1.16 ± 1.98 mm between centrelines of biliary ducts and liver veins, respectively. A workflow for automatic segmentation of the liver, hepatic vasculature and biliary anatomy from a single diagnostic MRI acquisition was developed. This enables automated extraction of 3D models of patient-specific liver anatomy, and may facilitating better perception of organ's anatomy during preparation and execution of liver surgeries. Additionally, it may help to reduce the incidence of intraoperative biliary duct damage due to an unanticipated variation in the anatomy.

Clinical Implementation of In-House Developed MR-Based Patient-Specific 3D Models of Liver Anatomy.

Knowledge of patient-specific liver anatomy is key to patient safety during major hepatobiliary surgery. Three-dimensional (3D) models of patient-specific liver anatomy based on diagnostic MRI images can provide essential vascular and biliary anatomical insight during surgery. However, a method for generating these is not yet publicly available. This paper describes how these 3D models of the liver can be generated using open source software, and then subsequently integrated into a sterile surgical environment. The most common image quality aspects that degrade the quality of the 3D models as well possible ways of eliminating these are also discussed. Per patient, a single diagnostic multiphase MRI scan with hepatospecific contrast agent was used for automated segmentation of liver contour, arterial, portal, and venous anatomy, and the biliary tree. Subsequently, lesions were delineated manually. The resulting interactive 3D model could be accessed during surgery on a sterile covered tablet. Up to now, such models have been used in 335 surgical procedures. Their use simplified the surgical treatment of patients with a high number of liver metastases and contributed to the localization of vanished lesions in cases of a radiological complete response to neoadjuvant treatment. They facilitated perioperative verification of the relationship of tumors and the surrounding vascular and biliary anatomy, and eased decision-making before and during surgery.

Feasibility and accuracy of quantitative imaging on a 1.5 T MR-linear accelerator.

PURPOSE: Systems for magnetic resonance (MR-) guided radiotherapy enable daily MR imaging of cancer patients during treatment, which is of interest for treatment response monitoring and biomarker discovery using quantitative MRI (qMRI). Here, the performance of a 1.5 T MR-linac regarding qMRI was assessed on phantoms. Additionally, we show the feasibility of qMRI in a prostate cancer patient on this system for the first time. MATERIALS AND METHODS: Four 1.5 T MR-linac systems from four institutes were included in this study. T1 and T2 relaxation times, and apparent diffusion coefficient (ADC) maps, as well as dynamic contrast enhanced (DCE) images were acquired. Bland-Altman statistics were used, and accuracy, repeatability, and reproducibility were determined. RESULTS: Median accuracy for T1 ranged over the four systems from 2.7 to 14.3%, for T2 from 10.4 to 14.1%, and for ADC from 1.9 to 2.7%. For DCE images, the accuracy ranged from 12.8 to 35.8% for a gadolinium concentration of 0.5 mM and deteriorated for higher concentrations. Median short-term repeatability for T1 ranged from 0.6 to 5.1%, for T2 from 0.4 to 1.2%, and for ADC from 1.3 to 2.2%. DCE acquisitions showed a coefficient of variation of 0.1-0.6% in the signal intensity. Long-term repeatability was 1.8% for T1, 1.4% for T2, 1.7% for ADC, and 17.9% for DCE. Reproducibility was 11.2% for T1, 2.9% for T2, 2.2% for ADC, and 18.4% for DCE. CONCLUSION: These results indicate that qMRI on the Unity MR-linac is feasible, accurate, and repeatable which is promising for treatment response monitoring and treatment plan adaptation based on daily qMRI.

Gas-induced susceptibility artefacts on diffusion-weighted MRI of the rectum at 1.5 T - Effect of applying a micro-enema to improve image quality.

PURPOSE: Assess whether application of a micro-enema can reduce gas-induced susceptibility artefacts in Single-shot Echo Planar Imaging (EPI) Diffusion-weighted imaging of the rectum at 1.5 T. MATERIALS AND METHODS: Retrospective analysis of n = 50 rectal cancer patients who each underwent multiple DWI-MRIs (1.5 T) from 2012 to 2016 as part of routine follow-up during a watch-and-wait approach after chemoradiotherapy. From March 2014 DWI-MRIs were routinely acquired after application of a preparatory micro-enema (Microlax®; 5 ml; self-administered shortly before acquisition); before March 2014 no bowel preparation was given. In total, 335 scans were scored by an experienced reader for the presence/severity of gas-artefacts (on b1000 DWI), ranging from 0 (no artefact) to 5 (severe artefact). A score ≥3 (moderate-severe) was considered a clinically relevant artefact. A random sample of 100 scans was re-assessed by a second independent reader to study inter-observer effects. Scores were compared between the scans performed without and with a preparatory micro-enema using univariable and multivariable logistic regression taking into account potential confounding factors (age/gender, acquisition parameters, MRI-hardware, rectoscopy prior to MRI). RESULTS: Clinically relevant gas-artefacts were seen in 24.3% (no micro-enema) vs. 3.7% (micro-enema), odds ratios were 0.118 in univariable and 0.230 in multivariable regression (P = 0.0005 and 0.0291). Mean severity score (±SD) was 1.19 ±â€¯1.71 (no-enema) vs 0.32 ±â€¯0.77 (micro-enema), odds ratios were 0.321 (P < 0.0001) and 0.489 (P = 0.0461) in uni- and multivariable regression, respectively. Inter-observer agreement was excellent (κ0.85). CONCLUSION: Use of a preparatory micro-enema shortly before rectal EPI-DWI examinations performed at 1.5 T MRI significantly reduces both the incidence and severity of gas-induced artefacts, compared to examinations performed without bowel preparation.

Supine Breast MRI Using Respiratory Triggering.

RATIONALE AND OBJECTIVES: This study aims to evaluate if navigator-echo respiratory-triggered magnetic resonance acquisition can acquire supine high-quality breast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Supine respiratory-triggered magnetic resonance imaging (Trig-MRI) was compared to supine non-Trig-MRI to evaluate breathing-induced motion artifacts (group 1), and to conventional prone non-Trig-MRI (group 2, 16-channel breast coil), all at 3T. A 32-channel thorax coil was placed on top of a cover to prevent breast deformation. Ten volunteers were scanned in each group, including one patient. The acquisition time was recorded. Image quality was compared by visual examination and by calculation of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and image sharpness (IS). RESULTS: Scan time increased from 56.5 seconds (non-Trig-MRI) to an average of 306 seconds with supine Trig-MRI (range: 120-540 seconds). In group 1, the median values (interquartile range) of SNR, CNR, and IS improved from 11.5 (6.0), 7.3 (3.1), and 0.23 (0.2) cm on supine non-Trig-MRI to 38.1 (29.1), 32.8 (29.7), and 0.12 (0) cm (all P < 0.01) on supine Trig-MRI. All qualitative image parameters in group 1 improved on supine Trig-MRI (all P < 0.01). In group 2, SNR and CNR improved from 14.7 (6.8) and 12.6 (5.6) on prone non-Trig-MRI to 36.2 (12.2) and 32.7 (12.1) (both P < 0.01) on supine Trig-MRI. IS was similar: 0.10 (0) cm vs 0.11 (0) cm (P = 0.88). CONCLUSIONS: Acquisition of high-quality supine breast MRI is possible when respiratory triggering is applied, in a similar setup as during subsequent treatment. Image quality improved when compared to supine non-triggered breast MRI and prone breast MRI, but at the cost of increased acquisition time.

Magnetic resonance elastography for the noninvasive staging of liver fibrosis.

BACKGROUND & AIMS: The purpose of our study was to prospectively compare the success rate and diagnostic accuracy of magnetic resonance elastography, ultrasound elastography, and aspartate aminotransferase to platelets ratio index (APRI) measurements for the noninvasive staging of fibrosis in patients with chronic liver disease. METHODS: We performed a prospective blind comparison of magnetic resonance elastography, ultrasound elastography, and APRI in a consecutive series of patients who underwent liver biopsy for chronic liver disease in a university-based hospital. Histopathologic staging of liver fibrosis according to the METAVIR scoring system served as the reference. RESULTS: A total of 141 patients were assessed. The technical success rate of magnetic resonance elastography was higher than that of ultrasound elastography (133/141 [94%] vs 118/141 [84%]; P = .016). Magnetic and ultrasound elastography, APRI measurements, and histopathologic analysis of liver biopsy specimens were technically successful in 96 patients. The areas under the receiver operating characteristic curves of magnetic resonance elasticity (0.994 for F >or= 2; 0.985 for F >or= 3; 0.998 for F = 4) were larger (P < .05) than those of ultrasound elasticity, APRI, and the combination of ultrasound elasticity and APRI (0.837, 0.709, and 0.849 for F >or= 2; 0.906, 0.816, and 0.936 for F >or= 3; 0.930, 0.820, and 0.944 for F = 4, respectively). CONCLUSIONS: Magnetic resonance elastography has a higher technical success rate than ultrasound elastography and a better diagnostic accuracy than ultrasound elastography and APRI for staging liver fibrosis.

Liver fibrosis: noninvasive assessment with MR elastography versus aspartate aminotransferase-to-platelet ratio index.

PURPOSE: To prospectively compare the sensitivity and specificity of magnetic resonance (MR) elastography with those of the routinely available aspartate aminotransferase-to-platelet ratio index (APRI) test for staging hepatic fibrosis in patients who have undergone liver biopsy for suspicion of chronic liver disease, with histopathologic examination as the reference standard. MATERIALS AND METHODS: The study was approved by the ethics committee. All patients gave written informed consent. Eighty-eight patients (37 men, 51 women; mean age, 54.0 years +/- 13.1 [standard deviation]) who underwent liver biopsy for suspicion of chronic liver disease underwent MR elastography and APRI testing within 2 days after liver biopsy. At histopathologic examination, the fibrosis stage was assessed according to METAVIR scores (fibrosis scores F0 [no fibrosis] to F4 [cirrhosis]). MR elastography was performed by transmitting mechanical waves within the liver and measuring the small cyclic displacement of the liver spins with a phase-contrast spin-echo sequence. The performances of MR elastography and APRI testing were assessed, and the optimal cutoff values for fibrosis stage were determined with receiver operating characteristic (ROC) curve analysis. RESULTS: At MR elastography, areas under the ROC curves (A(z)) for elasticity and viscosity, respectively, were 0.999 and 0.863 at fibrosis scores greater than or equal to F2, 0.997 and 0.962 at scores greater than or equal to F3, and 1.000 and 0.986 at score F4. A(z) values for elasticity at MR were significantly larger than those for the APRI (0.854 at scores > or = F2, P < .001; 0.886 at scores > or = F3, P = .003; and 0.851 at score F4, P = .004). Optimal cutoff values of elasticity were 2.5 kPa for fibrosis scores greater than or equal to F2, 3.1 kPa for scores greater than or equal to F3, and 4.3 kPa for score F4. CONCLUSION: Large A(z) values for elasticity (>0.990 for scores > or = F2, > or = F3, and F4) show that MR elastography was accurate in liver fibrosis staging and superior to biochemical testing with APRIs.

Liver fibrosis: non-invasive assessment with MR elastography.

The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis. Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study. The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0, no fibrosis, to F4, cirrhosis. MR elastography was performed by transmitting low-frequency (65 Hz) mechanical waves into the liver with a transducer placed at the back of the patients. The MR pulse sequence was a motion-sensitized spin-echo sequence, phase-locked to the mechanical excitation. The phase maps were processed to obtain shear elasticity and shear viscosity maps. The mean hepatic shear elasticity increased with increasing stage of fibrosis. The mean elasticity was 2.24 +/- 0.23 kPa in the 11 patients without substantial fibrosis (F0-F1 grades), 2.56 +/- 0.24 kPa in the four patients with substantial fibrosis (F2-F3) and 4.68 +/- 1.61 kPa in the 10 patients with cirrhosis (F4). The differences between groups were statistically significant (p