Diffusion-weighted Magnetic Resonance Imaging Scans Research Articles

Prevalence of oligoprogression in metastatic hormone-resistant prostate cancer patients on androgen targeted therapies: Could targeted radiotherapy improve patient outcomes?

110 Background: Androgen receptor-targeted therapies (ART) such as Abiraterone and Enzalutamide have shifted the management paradigm of metastatic castrate-resistant prostate cancer (mCRPC). These treatments are well-tolerated with less toxicities compared to chemotherapy, therefore methods to delay chemotherapy are beneficial to patients. Patients eventually become resistant to ARTs, and some patients will progress in a limited number of sites. This study investigated the prevalence of oligoprogressive disease (OPD) amenable to Stereotactic-body radiotherapy (SBRT). OPD is defined as ≤3 metastatic lesions which are progressing or new whilst all other sites of disease are well-controlled by ART. Methods: Retrospective analysis of electronic patient records and imaging studies of 95 patients treated with ART for mCRPC between April 2015 – 2017 from a single centre was undertaken. Data was analysed at the time of first tumour progression on ART. Results: The median (IQR) age of patients was 78.8 (74.4-83.6) years. OPD was found in 27 (28%) patients, 18 (19%) had lesions suitable for SBRT (Table). Seventeen (63%) patients were treated with abiraterone, 10 (27%) patients with enzalutamide. Median (IQR) time from starting ART to OPD was 16.4 (8.6-19.9) months. Five (19%) patients had 3 sites of OPD, 8 (29%) patients had 2 sites of OPD and 14 (52%) patients had 1 site of OPD. Nineteen patients continued ART beyond OPD for ≥3months. OPD was diagnosed using CT scan (56%), whole body diffusion-weighted MRI (22%), choline PET/CT (19%) and bone scan (3%). Six (22%) patients were treated with radiotherapy for OPD, 3 as participants of the TRAP trial (NCT03644303). Median time to subsequent progression after OPD for the 3 patients treated off trial with radiotherapy was 20.5 months. The OPD lesions treated with radiotherapy included the prostate (2 patients, 30 Gy in 5 and 24 Gy in 4 fractions) and para-aortic lymph node (1 patient, 30 Gy in 5 fractions). Median time to subsequent progression after OPD for those who did not receive radiotherapy was 6.4 months. There was no significant difference between median overall survival between patients with OPD and those who progressed with > 3 lesions (7 vs 9.2 years, P= 0.54). Ten (66%) patients who progressed after initial OPD on continuation of ART progressed with further OPD (≤3 lesions including original OPD lesion). Conclusions: OPD is prevalent in patients on ART for mCRPC. The most frequent site of OPD was in bone and majority of patients had only 1 site of OPD at presentation. These results identify a cohort of patients who may benefit from SBRT to maximise ART treatment. Fourteen (14%) patients met entry criteria for TRAP trial which is currently testing the role of SBRT to sites of OPD in mCRPC. [Table: see text]

Contrast-Free Detection of Focused Ultrasound-Induced Blood-Brain Barrier Opening Using Diffusion Tensor Imaging.

Focused ultrasound (FUS) has emerged as a non-invasive technique to locally and reversibly disrupt the blood-brain barrier (BBB). Here, we investigate the use of diffusion tensor imaging (DTI) as a means of detecting FUS-induced BBB opening at the absence of an MRI contrast agent. A non-human primate (NHP) was repeatedly treated with FUS and preformed circulating microbubbles to transiently disrupt the BBB (n = 4). T1- and diffusion-weighted MRI scans were acquired after the ultrasound treatment, with and without gadolinium-based contrast agent, respectively. Both scans were registered with a high-resolution T1-weighted scan of the NHP to investigate signal correlations. DTI detected an increase in fractional anisotropy from 0.21 ± 0.02 to 0.38 ± 0.03 (82.6 ± 5.2% change) within the targeted area one hour after BBB opening. Enhanced DTI contrast overlapped by 77.22 ± 9.2% with hyper-intense areas of gadolinium-enhanced T1-weighted scans, indicating diffusion anisotropy enhancement only within the BBB opening volume. Diffusion was highly anisotropic and unidirectional within the treated brain region, as indicated by the direction of the principal diffusion eigenvectors. Polar and azimuthal angle ranges decreased by 35.6% and 82.4%, respectively, following BBB opening. Evaluation of the detection methodology on a second NHP (n = 1) confirmed the across-animal feasibility of the technique. In conclusion, DTI may be used as a contrast-free MR imaging modality in lieu of contrast-enhanced T1 mapping for detecting BBB opening during focused-ultrasound treatment or evaluating BBB integrity in brain-related pathologies.

Voxelwise and Regional Brain Apparent Diffusion Coefficient Changes on MRI from Birth to 6 Years of Age.

Background A framework for understanding rapid diffusion changes from 0 to 6 years of age is important in the detection of neurodevelopmental disorders. Purpose To quantify patterns of normal apparent diffusion coefficient (ADC) development from 0 to 6 years of age. Materials and Methods Previously constructed age-specific ADC atlases from 201 healthy full-term children (108 male; age range, 0-6 years) with MRI scans acquired from 2006 to 2013 at one large academic hospital were analyzed to quantify four patterns: ADC trajectory, rate of ADC change, age of ADC maturation, and hemispheric asymmetries of maturation ages. Patterns were quantified in whole-brain, segmented regional, and voxelwise levels by fitting a two-term exponential model. Hemispheric asymmetries in ADC maturation ages were assessed using t tests with Bonferroni correction. Results The posterior limb of the internal capsule (mean ADC: left hemisphere, 1.18 ×103μm2/sec; right hemisphere, 1.17 ×103μm2/sec), anterior limb of the internal capsule (left, 1.11 ×103μm2/sec; right, 1.09 ×103μm2/sec), vermis (1.26 ×103μm2/sec), thalami (left, 1.17 ×103μm2/sec; right, 1.15 ×103μm2/sec), and basal ganglia (left, 1.26 ×103μm2/sec; right, 1.23 ×103μm2/sec) demonstrate low initial ADC values, indicating an earlier prenatal time course of development. ADC maturation was completed between 1.3 and 2.4 years of age, depending on the region. The vermis and left thalamus matured earliest (1.3 years). The frontolateral gray matter matured latest (right, 2.3 years; left, 2.4 years). ADC maturation occurred earlier in the left hemisphere (P < .001) in several regions, including the frontal (mean ± standard deviation) (left, 2.16 years ± 0.29; right, 2.19 years ± 0.31), temporal (left, 1.93 years ± 0.22; right, 1.99 years ± 0.22), and parietal (left, 1.92 years ± 0.30; right, 2.03 years ± 0.28) white matter. Maturation occurred earlier in the right hemisphere (P < .001) in several regions, including the thalami (left, 1.63 years ± 0.32; right, 1.45 years ± 0.33), basal ganglia (left, 1.79 years ± 0.31; right, 1.70 years ± 0.37), and hippocampi (left, 1.93 years ± 0.34; right, 1.78 years ± 0.33). Conclusion Normative apparent diffusion coefficient developmental patterns on diffusion-weighted MRI scans were quantified in children aged 0 to 6 years. This work provides knowledge about early brain development and may guide the detection of abnormal patterns of maturation. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Rollins in this issue.

Integration of brain and behavior measures for identification of data-driven groups cutting across children with ASD, ADHD, or OCD.

Autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) are clinically and biologically heterogeneous neurodevelopmental disorders (NDDs). The objective of the present study was to integrate brain imaging and behavioral measures to identify new brain-behavior subgroups cutting across these disorders. A subset of the data from the Province of Ontario Neurodevelopmental Disorder (POND) Network was used including participants with different NDDs (aged 6-16 years) that underwent cross-sectional T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) scanning on the same 3T scanner, and behavioral/cognitive assessments. Similarity Network Fusion was applied to integrate cortical thickness, subcortical volume, white matter fractional anisotropy (FA), and behavioral measures in 176 children with ASD, ADHD or OCD with complete data that passed quality control. Normalized mutual information was used to determine top contributing model features. Bootstrapping, out-of-model outcome measures and supervised machine learning were each used to examine stability and evaluate the new groups. Cortical thickness in socio-emotional and attention/executive networks and inattention symptoms comprised the top ten features driving participant similarity and differences between four transdiagnostic groups. Subcortical volumes (pallidum, nucleus accumbens, thalamus) were also different among groups, although white matter FA showed limited differences. Features driving participant similarity remained stable across resampling, and the new groups showed significantly different scores on everyday adaptive functioning. Our findings open the possibility of studying new data-driven groups that represent children with NDDs more similar to each other than others within their own diagnostic group. Future work is needed to build on this early attempt through replication of the current findings in independent samples and testing longitudinally for prognostic value.

Randomized clinical trial comparing a rivaroxaban-based with an antiplatelet-based strategy for cerebral embolization after TAVR (EARTH TAVR)-a magnetic resonance imaging substudy of the GALILEO trial

Abstract Background Cerebral embolization in patients after Transcatheter Aortic Valve Replacement (TAVR) represents a serious complication, that was related to impaired bioprosthetic leaflet motion and new-onset atrial fibrillation (AFib). Purpose Hereafter we present the first randomized study comparing the effect of an anticoagulation plus antiplatelet with a dual antiplatelet antithrombotic treatment in patients after TAVR on cerebral embolizations as assessed by serial cerebral magnetic resonance imaging (MRI). Methods The Evaluation of Cerebral Thrombembolism After TAVR (EARTH - TAVR) study was conducted as an investigator initiated substudy of the multicenter, randomized, GALILEO study. After successful TAVR, patients without indication for chronic anticoagulation were randomly assigned to rivaroxaban 10mg plus acetylsalicylic acid 75–100mg once-daily or clopidogrel 75mg plus acetylsalicylic acid 75–100mg once-daily. Cerebral MRI scans were performed pre-TAVR as a baseline, post-TAVR (within 24–48 hours after TAVR) and 90 days after TAVR. The MRI protocol included diffusion-weighted (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging. Cerebral embolic lesions were evaluated by an independent cerebral MRI core lab. The primary outcome measure of this study was the occurrence and extent of cerebral embolizations as measured by total volume of new ischaemic cerebral lesions. Results 36 patients were enrolled in the EARTH and the GALILEO study. The DWI MRI scans revealed an increase of cerebral lesions and volume post-TAVR by a median of 4.75 (95% NBCI 2.1–8.9) and 0.26cm3 (95% NBCI 0.11–0.59). On FLAIR imaging, lesion number and volume increased by a median of 3 (95% NBCI 1.5–6) and 0.1 cm3 (95% NBCI 0.04–0.31). At the 90 days MRI scan, there was no statistically significant change in cerebral lesions, if compared to the post-TAVR scan, irrespective of the treatment arm. Conclusion Thromboembolic events occur largely in the periinterventional phase post TAVR. Thereafter, the risk for additional cerebral embolization is low. An additional rivaroxaban therapy beyond antiplatelet inhibition did not impact on cerebral thromboembolism. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Pharmaceuticals

White matter microstructure and connectivity in patients with obsessive‐compulsive disorder and their unaffected siblings

We aimed to examine white matter microstructure and connectivity in individuals with obsessive-compulsive disorder (OCD) and their unaffected siblings, relative to healthy controls. Diffusion-weighted magnetic resonance imaging (dMRI) scans were acquired in 30 patients with OCD, 21 unaffected siblings, and 31 controls. We examined white matter microstructure using measures of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Structural networks were examined using network-based statistic (NBS). Compared to controls, OCD patients showed significantly reduced FA and increased RD in clusters traversing the left forceps minor, inferior fronto-occipital fasciculus, anterior thalamic radiation, and cingulum. Furthermore, the OCD group displayed significantly weaker connectivity (quantified by the streamline count) compared to controls in the right hemisphere, most notably in edges connecting subcortical structures to temporo-occipital cortical regions. The sibling group showed intermediate streamline counts, FA and RD values between OCD and healthy control groups in connections found to be abnormal in patients with OCD. However, these reductions did not significantly differ compared to controls. Therefore, siblings of OCD patients display intermediate levels in dMRI measures of microstructure and connectivity, suggesting white matter abnormalities might be related to the familial predisposition for OCD.

The relation between neurofunctional and neurostructural determinants of phonological processing in pre-readers

Phonological processing skills are known as the most robust cognitive predictor of reading ability. Therefore, the neural determinants of phonological processing have been extensively investigated by means of either neurofunctional or neurostructural techniques. However, to fully understand how the brain represents and processes phonological information, there is need for studies that combine both methods. The present study applies such a multimodal approach with the aim of investigating the pre-reading relation between neural measures of auditory temporal processing, white matter properties of the reading network and phonological processing skills. We administered auditory steady-state responses, diffusion-weighted MRI scans and phonological awareness tasks in 59 pre-readers. Our results demonstrate that a stronger rightward lateralization of syllable-rate (4 Hz) processing coheres with higher fractional anisotropy in the left fronto-temporoparietal arcuate fasciculus. Both neural features each in turn relate to better phonological processing skills. As such, the current study provides novel evidence for the existence of a pre-reading relation between functional measures of syllable-rate processing, structural organization of the arcuate fasciculus and cognitive precursors of reading development. Moreover, our findings demonstrate the value of combining different neural techniques to gain insight in the underlying neural systems for reading (dis)ability.

Cardiovascular risk factors and APOE‐ε4 status affect memory functioning in aging via changes to temporal stem diffusion

Prior research investigating associations between hypertension, obesity, and apolipoprotein (APOE) genotype status with memory performance among older adults has yielded inconsistent results. This may reflect, in part, a lack of first accounting for the effects these variables have on structural brain changes, that in turn contribute to age-related memory impairment. The current study sought to clarify the relationships between these factors via path modeling. We hypothesized that higher body mass index (BMI), hypertension, and being an APOE-ε4 allele carrier would predict poorer memory scores, with much of these effects accounted for by indirect effects operating via differences in the integrity of temporal stem white matter. Participants included 125 healthy older adults who underwent neuropsychological assessment and diffusion-weighted MRI scanning. Direct effects were found for hypertension and demographic variables including age, sex, and education. Importantly, indirect effects were found for BMI, hypertension, APOE-ε4 status, age, and sex, where these factors predicted memory scores via their impact on temporal stem diffusion measures. There was also a dual effect of sex, with a direct effect indicating that females had better memory performance overall, and an indirect effect indicating that females with greater temporal stem diffusion had poorer memory performance. Results suggest that changes to the integrity of temporal white matter in aging may underpin reduced memory performance. These results highlight that accounting for variables that not only directly impact cognition, but also for those that indirectly impact cognition via structural brain changes, is crucial for understanding the impact of risk factors on cognition.

A Prospective Study of Diffusion-weighted Magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus

AimsThe use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a prognostic marker of treatment response would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent diffusion coefficient (ΔADCmean) between a DW-MRI at diagnosis and on fraction 8–10 of chemoradiotherapy (CRT) as a biomarker for cellularity, and correlate these with anal squamous cell carcinoma recurrence. Materials and methodsThis prospective study recruited patients with localised anal cancer between October 2014 and November 2017. DW-MRI was carried out at diagnosis and after fraction 8–10 of radical CRT. A region of interest was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T2-weighted images and propagated to the ADC map. Routine clinical follow-up was collected from Nation Health Service electronic systems. ResultsTwenty-three of 29 recruited patients underwent paired DW-MRI scans. Twenty-six regions of interest were delineated among the 23 evaluable patients. The median (range) tumour volume was 13.6 cm3 (2.8–84.9 cm3). Ten of 23 patients had lesions with ΔADCmean ≤ 20%. With a median follow-up of 41.2 months, four patients either failed to have a complete response to CRT or subsequently relapsed. Three of four patients with disease relapse had lesions demonstrating ΔADCmean <20%, the other patient with persistent disease had ΔADCmean of 20.3%. ConclusionsWe demonstrated a potential correlation between patients with ΔADCmean <20% and disease relapse. Further investigation of the prognostic merit of DW-MRI change is needed in larger, prospective cohorts.

Predictive value of T2-weighted magnetic resonance imaging for the prognosis of patients with mass-type breast cancer with peritumoral edema.

The aim of the present study was to investigate the role of edema surrounding breast cancer masses in the prognostic prediction of magnetic resonance imaging (MRI) T2-weighted fat suppression sequence. For this purpose, 80 patients with mass-type breast cancer underwent conventional plain breast MRI, dynamic contrast-enhanced (DCE)-MRI or diffusion-weighted MRI scan. The associations between edema around the mass on MRI T2 fat suppression sequence plain scan and tumor stage, pathological findings, immunohistochemical findings and axillary lymph node metastasis were analyzed. The results revealed the presence of edema around the mass on the MRI T2 fat suppression sequence plain scan in 35 patients. By contrast, there was no abnormal enhancement on the DCE-MRI, and the apparent diffusion coefficient value did not decrease in these areas. Compared with the remaining 45 patients, the 35 patients with peritumoral edema exhibited a higher tumor stage and a higher rate of axillary lymph node metastasis (all P<0.05). However, there was no significant difference in pathological classification or the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (as determined by immunohistochemistry) between the two groups. In total, 12 cases of tumor shrinkage during neoadjuvant chemotherapy were accompanied by an improvement in edema. Taken together, the findings of the present study indicated that the presence of edema around the mass on the MRI T2 fat suppression sequence may predict poor prognosis in patients with mass-type breast cancer. Furthermore, the improvement of the peritumoral edema post-neoadjuvant chemotherapy may also be a predictor of a more favorable prognosis.

Standard Diffusion-weighted MRI for the Diagnosis of Central Retinal Artery Occlusion

PurposeTo evaluate diffusion abnormalities of the retina and optic nerve in patients with central retinal artery occlusion (CRAO) using standard stroke diffusion-weighted magnetic resonance imaging (DWI).MethodsIn this case-control study, DWI scans of patients with nonarteritic CRAO were retrospectively assessed for acute ischemia of the retina and optic nerve. Two neuroradiologists, blinded for patient diagnosis, randomly evaluated DWI of CRAO patients and controls (a collective of stroke and transient ischemic attack [TIA] patients) for restrictions of the retina and optic nerve. We calculated statistical quality criteria and analyzed inter-rater reliability using unweighted Kappa statistics.Results20 CRAO patients (60,6 ± 17 years) and 20 controls (60,7 ± 17 years) were included in the study. Sensitivity, specificity, positive and negative predictive values for retinal DWI restrictions were 75%/80%/79%/76% (reader 1) and 75%/100%/100%/80% (reader 2), respectively. Unweighted Kappa was κ = 0,70 (95% CI 0,48‑0,92), indicating “substantial” interrater reliability. In comparison, sensitivity, specificity, PPV and NPV (positive and negative predictive values) for restrictions of the optic nerve in CRAO were 55%/70%/65%/61% (reader 1) and 25%/100%/100%/57% (reader 2). Inter-rater reliability was “fair” with unweighted Kappa κ = 0,32 (95% CI 0,09‑0,56).ConclusionsRetinal diffusion restrictions were present in a majority of CRAO patients and detectable with reasonable sensitivity, high specificity and substantial inter-rater reliability. Further studies are necessary to study time dependency of retinal diffusion restrictions, improve image quality and investigate the reliability of retinal DWI to discern CRAO from other causes of acute loss of vision.

Reduced tract length of the medial forebrain bundle and the anterior thalamic radiation in bipolar disorder with melancholic depression

BackgroundThe supero-lateral medial forebrain bundle (slMFB) and the anterior thalamic radiation (ATR) play a core role in reward anticipation and motivational processes. In this study, the slMFB and the ATR were investigated in a group of depressed bipolar disorder (BD) and in healthy controls (HC) using tract length as a measure of fibre geometry and fractional anisotropy (FA) as a measure of white matter microstructure. We hypothesized reduced tract length and FA of the slMFB and the ATR in BD. We expect alterations to be driven by the melancholic subtype. MethodsNineteen depressed patients with BD and 19 HC matched for age and gender underwent diffusion-weighted magnetic resonance imaging (MRI) scans. Diffusion tensor imaging (DTI) based tractography was used to reconstruct bilateral slMFB and ATR. Mean tract length and FA were computed for the slMFB and the ATR. Mixed-model ANCOVAs and post-hoc ANCOVAs, controlling for age and intracranial volume, were used to compare tract length and FA of bilateral slMFB and ATR between HC and BD and between HC and subgroups with melancholic and non-melancholic symptoms. ResultsIn BD we found a significantly shortened tract length of the right slMFB and ATR in BD compared to HC. Subgroup analyses showed that these findings were driven by the melancholic subgroup. Mean-FA did not differ between HC and BD. LimitationsSample size ConclusionsTract length of the right slMFB and the right ATR is reduced in BD. Those changes of fibre geometry are driven by the melancholic subtype.

The Impact of Perioperative Arterial Infarct on Recurrence, Functional Outcomes, and Survival in Glioblastoma Patients.

Background: Perioperative infarcts are a known complication that can occur during the resection of glioblastoma (GBM). Recent studies suggest that gross total and even “supra-total” resections may be associated with an increased survival but the rate of complications, including perioperative ischemia, may increase with these more aggressive resection strategies. However, little is known about the impact that perioperative infarcts have on survival, functional outcomes, and tumor recurrence patterns. Our study attempted to quantify and characterize the functional consequences of a perioperative infarct, as well as risk factors associated with occurrence.Methods: Seventy-three patients with a diagnosis of GBM and perioperative ischemia by MRI were identified from the electronic medical record system. We obtained demographic, prognostic, and stroke risk factor data. Infarct volumes were calculated from diffusion-weighted MRI scans, and subjects were segregated into an infarct cohort or a control cohort based on whether the identified lesion appeared to be an infarct in an arterial distribution or instead appeared to be expected postoperative changes. A multivariate statistical analysis was performed on the dataset.Results: Median age was 58.6 years, median post-op KPS (Karnofsky Performance Status) was 90, and median extent of resection (based on MRI) was 97.8%. Overall, perioperative arterial infarcts were uncommon (2.0%), did not have a statistically significant impact on survival (17.9 vs. 18.9 months), did not worsen neurologic function, and did not alter the pattern of recurrence.Conclusion: Perioperative arterial infarcts were uncommon in our patients despite aggressive resection and when present had no impact on survival or neurologic function. Given the clear benefit of maximal tumor resection, the risk of perioperative infarct should not deter maximal safe resection.

A multimodal computer‐aided diagnostic system for precise identification of renal allograft rejection: Preliminary results

Early assessment of renal allograft function post-transplantation is crucial to minimize and control allograft rejection. Biopsy - the gold standard - is used only as a last resort due to its invasiveness, high cost, adverse events (e.g., bleeding, infection, etc.), and the time for reporting. To overcome these limitations, a renal computer-assisted diagnostic (Renal-CAD) system was developed to assess kidney transplant function. The developed Renal-CAD system integrates data collected from two image-based sources and two clinical-based sources to assess renal transplant function. The imaging sources were the apparent diffusion coefficients (ADCs) extracted from 47 diffusion-weighted magnetic resonance imaging (DW-MRI) scans at 11 different b-values (b0, b50, b100, ..., b1000 s/mm ), and the transverse relaxation rate (R2*) extracted from 30 blood oxygen level-dependent MRI (BOLD-MRI) scans at 5 different echo times (TEs=2, 7, 12, 17, and 22ms). Serum creatinine (SCr) and creatinine clearance (CrCl) were the clinical sources for kidney function evaluation. The Renal-CAD system initially performed kidney segmentation using the level-set method, followed by estimation of the ADCs from DW-MRIs and the R2* from BOLD-MRIs. ADCs and R2* estimates from 30 subjects that have both types of scans were integrated with their associated SCr and CrCl. The integrated biomarkers were then used as our discriminatory features to train and test a deep learning-based classifier, namely stacked autoencoders (SAEs) to differentiate non-rejection (NR) from acute rejection (AR) renal transplants. Using a leave-one-subject-out cross-validation approach along with SAEs, the Renal-CAD system demonstrated 93.3% accuracy, 90.0% sensitivity, and 95.0% specificity in differentiating AR from NR. Robustness of the Renal-CAD system was also confirmed by the area under the curve value of 0.92. Using a stratified tenfold cross-validation approach, the Renal-CAD system demonstrated its reproducibility and robustness by a diagnostic accuracy of 86.7%, sensitivity of 80.0%, specificity of 90.0%, and AUC of 0.88. The obtained results demonstrate the feasibility and efficacy of accurate, noninvasive identification of AR at an early stage using the Renal-CAD system.

Ex vivo diffusion-weighted MRI tractography of the Göttingen minipig limbic system.

The limbic system encompasses a collection of brain areas primarily involved in higher cognitive and emotional processing. Altered function in the limbic circuitry may play a major role in various psychiatric disorders. This study aims to provide a high-quality ex vivo diffusion-weighted MRI (DWI) tractographic overview of the Göttingen minipig limbic system pathways, which are currently not well described. This may facilitate future translational large animal studies. The study used previously obtained post-mortem DWI scans in 3 female Göttingen minipigs aging 11-15months. The tractography performed on the DWI data set was made using a probabilistic algorithm, and regions of interest (ROIs) were defined in accordance with a histological atlas. The investigated pathways included the fornix, mammillothalamic tract, stria terminalis, stria medullaris, habenulo-interpeduncular tract, and cingulum. All the investigated limbic connections could be visualized with a high detail yielding a comprehensive three-dimensional overview, which was emphasized by the inclusion of video material. The minipig limbic system pathways displayed using tractography closely resembled what was previously described in both human studies and neuronal tracing studies from other mammalian species. We encountered well-known inherent methodological challenges of tractography, e.g., partial volume effects and complex white matter regions, which may have contributed to derouted false-positive streamlines and the failure to visualize some of the minor limbic pathway ramifications. This underlines the importance of preexisting anatomical knowledge. Conclusively, we have, for the first time, provided an overview and substantial insight of the Göttingen minipig limbic system.

Machine Learning for Detecting Early Infarction in Acute Stroke with Non-Contrast-enhanced CT.

Background Identifying the presence and extent of infarcted brain tissue at baseline plays a crucial role in the treatment of patients with acute ischemic stroke (AIS). Patients with extensive infarction are unlikely to benefit from thrombolysis or thrombectomy procedures. Purpose To develop an automated approach to detect and quantitate infarction by using non-contrast-enhanced CT scans in patients with AIS. Materials and Methods Non-contrast-enhanced CT images in patients with AIS (<6 hours from symptom onset to CT) who also underwent diffusion-weighted (DW) MRI within 1 hour after AIS were obtained from May 2004 to July 2009 and were included in this retrospective study. Ischemic lesions manually contoured on DW MRI scans were used as the reference standard. An automatic segmentation approach involving machine learning (ML) was developed to detect infarction. Randomly selected nonenhanced CT images from 157 patients with the lesion labels manually contoured on DW MRI scans were used to train and validate the ML model; the remaining 100 patients independent of the derivation cohort were used for testing. The ML algorithm was quantitatively compared with the reference standard (DW MRI) by using Bland-Altman plots and Pearson correlation. Results In 100 patients in the testing data set (median age, 69 years; interquartile range [IQR]: 59-76 years; 59 men), baseline non-contrast-enhanced CT was performed within a median time of 48 minutes from symptom onset (IQR, 27-93 minutes); baseline MRI was performed a median of 38 minutes (IQR, 24-48 minutes) later. The algorithm-detected lesion volume correlated with the reference standard of expert-contoured lesion volume in acute DW MRI scans (r = 0.76, P < .001). The mean difference between the algorithm-segmented volume (median, 15 mL; IQR, 9-38 mL) and the DW MRI volume (median, 19 mL; IQR, 5-43 mL) was 11 mL (P = .89). Conclusion A machine learning approach for segmentation of infarction on non-contrast-enhanced CT images in patients with acute ischemic stroke showed good agreement with stroke volume on diffusion-weighted MRI scans. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Nael in this issue.

Preoperative Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients With Esophageal Cancer Using 18F-FDG PET/CT and DW-MRI: A Prospective Multicenter Study

Accurate preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer could enable omission of esophagectomy in patients with a pathologic complete response (pCR). This study aimed to evaluate the individual and combined value of 18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (18F-FDG PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) during and after nCRT to predict pathologic response in patients with esophageal cancer. In this multicenter prospective study, patients scheduled to receive nCRT followed by esophagectomy for esophageal cancer underwent 18F-FDG PET/CT and DW-MRI scanning before the start of nCRT, during nCRT, and before esophagectomy. Response to nCRT was based on histopathologic evaluation of the resection specimen. Relative changes in 18F-FDG PET/CT and DW-MRI parameters were compared between patients with pCR and non-pCR groups. Multivariable ridge regression analyses with bootstrapped c-indices were performed to evaluate the individual and combined value of 18F-FDG PET/CT and DW-MRI. pCR was found in 26.1% of 69 patients. Relative changes in 18F-FDG PET/CT parameters after nCRT (Δ standardized uptake value [SUV]mean,postP = .016, and Δ total lesion glycolysis postP = .024), as well as changes in DW-MRI parameters during nCRT (Δ apparent diffusion coefficient [ADC]duringP = .008) were significantly different between pCR and non-pCR. A c-statistic of 0.84 was obtained for a model with ΔADCduring, ΔSUVmean,post, and histology in classifying patients as pCR (versus 0.82 for ΔADCduring and 0.79 for ΔSUVmean,post alone). Changes on 18F-FDG PET/CT after nCRT and early changes on DW-MRI during nCRT can help identify pCR to nCRT in esophageal cancer. Moreover, 18F-FDG PET/CT and DW-MRI might be of complementary value in the assessment of pCR.

Elevated Extracellular Free-Water in a Multicentric First-Episode Psychosis Sample, Decrease During the First 2 Years of Illness.

Recent diffusion imaging studies using free-water (FW) elimination have shown increased FW in gray matter (GM) and white matter (WM) in first-episode psychosis (FEP) and lower corrected fractional anisotropy (FAt) in WM in chronic schizophrenia. However, little is known about the longitudinal stability and clinical significance of these findings. To determine tissue-specific FW and FAt abnormalities in FEP, as part of a multicenter Spanish study, 132 FEP and 108 healthy controls (HC) were clinically characterized and underwent structural and diffusion-weighted MRI scanning. FEP subjects were classified as schizophrenia spectrum disorder (SSD) or non-SSD. Of these subjects, 45 FEP and 41 HC were longitudinally assessed and rescanned after 2 years. FA and FW tissue-specific measurements were cross-sectional and longitudinally compared between groups using voxel-wise analyses in the skeletonized WM and vertex-wise analyses in the GM surface. SSD and non-SSD subjects showed (a) higher baseline FW in temporal regions and in whole GM average (P.adj(SSD vs HC) = .003, P.adj(Non-SSD vs HC) = .040) and (b) lower baseline FAt in several WM tracts. SSD, but not non-SSD, showed (a) higher FW in several WM tracts and in whole WM (P.adj(SSD vs HC)= .049) and (b) a significant FW decrease over time in temporal cortical regions and in whole GM average (P.adj = .011). Increased extracellular FW in the brain is a reliable finding in FEP, and in SSD appears to decrease over the early course of the illness. FAt abnormalities are stable during the first years of psychosis.

Optimal timing for prediction of pathologic complete response to neoadjuvant chemoradiotherapy with diffusion-weighted MRI in patients with esophageal cancer

ObjectiveThis study was conducted in order to determine the optimal timing of diffusion-weighted magnetic resonance imaging (DW-MRI) for prediction of pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer.MethodsPatients with esophageal adenocarcinoma or squamous cell carcinoma who planned to undergo nCRT followed by surgery were enrolled in this prospective study. Patients underwent six DW-MRI scans: one baseline scan before the start of nCRT and weekly scans during 5 weeks of nCRT. Relative changes in mean apparent diffusion coefficient (ADC) values between the baseline scans and the scans during nCRT (ΔADC(%)) were compared between pathologic complete responders (pCR) and non-pCR (tumor regression grades 2–5). The discriminative ability of ΔADC(%) was determined based on the c-statistic.ResultsA total of 24 patients with 142 DW-MRI scans were included. pCR was observed in seven patients (29%). ΔADC(%) from baseline to week 2 was significantly higher in patients with pCR versus non-pCR (median [IQR], 36% [30%, 41%] for pCR versus 16% [14%, 29%] for non-pCR, p = 0.004). The ΔADC(%) of the second week in combination with histology resulted in the highest c-statistic for the prediction of pCR versus non-pCR (0.87). The c-statistic of this model increased to 0.97 after additional exclusion of patients with a small tumor volume (< 7 mL, n = 3) and tumor histology of the resection specimen other than adenocarcinoma or squamous cell carcinoma (n = 1).ConclusionThe relative change in tumor ADC (ΔADC(%)) during the first 2 weeks of nCRT is the most predictive for pathologic complete response to nCRT in esophageal cancer patients.Key Points• DW-MRI during the second week of neoadjuvant chemoradiotherapy is most predictive for pathologic complete response in esophageal cancer.• A model including ΔADCweek 2was able to discriminate between pathologic complete responders and non-pathologic complete responders in 87%.• Improvements in future MRI studies for esophageal cancer may be obtained by incorporating motion management techniques.

Final Trial Results of Repeated Diffusion-Weighted MRI and FDG-PET Imaging for the Prediction of Response to Chemoradiation Therapy in Esophageal Cancer

To present the final results of a prospective study to evaluate imaging predictors for pathologic complete response (pathCR) to chemoradiation therapy (CRT) in esophageal cancer using repeated diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging before, during, and after CRT. Between January 2014 and July 2017, 60 patients with stage II-III esophageal cancer were prospectively enrolled. DW-MRI and FDG-PET imaging were acquired before treatment (baseline), 12-14 days after initiation of CRT (interim, IM), and at first follow-up 4-6 weeks after completing CRT. The primary outcome was pathCR as assessed after subsequent surgery, with secondary outcomes evaluating locoregional and distant progression-free survival (LPFS and DPFS), and overall survival (OS) according to the imaging parameters. Logistic regression analysis was used to evaluate the association of primary tumor apparent diffusion coefficient (ADC) values, maximum and mean standardized uptake value (SUV), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) at baseline and their relative changes (Δ) at interim and follow-up scans with pathCR. Survival analyses applied to evaluate the association of the imaging parameters with LPFS, DPFS, and OS. Surgery after CRT was performed in 29 (48%) of 60 included patients. Imaging data was eligible for analysis in 28 patients in whom pathCR was observed in 7 (25%). The change in tumor mean ADC from the baseline to the interim DW-MRI scan, at a threshold of +27.7%, was best predictive for pathCR (c-statistic=0.98). The change in TLG from the baseline to interim FDG-PET scan, at a threshold of 58% decrease, was the best FDG-PET-based predictor of pathCR (c-statistic=0.77). Multivariable logistic regression suggested no significant added value of ΔTLGIM to ΔADCIM for the prediction of pathCR. Median follow-up was 29 months (range: 5-59) overall and 36 months (range: 24-59) for survivors. In surgical patients no locoregional progression was seen, and studied DW-MRI and FDG-PET parameters were not significantly associated with DPFS or OS. For non-surgical patients with ΔADCIM above vs below +27.7%, observed locoregional recurrence rates were 1/5 (20%) vs 7/25 (28%) (NS), and distant recurrence rates were 1/5 (20%) vs 15/25 (60%) (NS). For non-surgical patients with ΔTLGIM below vs above -58%, observed locoregional recurrence rates were 2/11 (18%) vs 5/17 (29%) (NS), and distant recurrence rates were 3/11 (27%) vs 12/17 (71%) (log-rank test, p=0.04). No association between imaging parameters and OS was observed. ΔADC on DW-MRI after 2 weeks of CRT strongly predicts pathologic complete response in esophageal cancer, with superior performance to repeated FDG-PET imaging. Early response assessment using DW-MRI is potentially useful for stratification of esophageal cancer patients to treatment intensification or organ-preserving strategies.