Baseline MRI Research Articles

Utility of Cortical Atrophy in Functional Networks as a Predictor of Progression in bvFTD

AbstractBackgroundBehavioral variant frontotemporal dementia (bvFTD) is a clinically heterogeneous neurodegenerative disorder with variable rates of disease progression. Predictors of disease progression in bvFTD are significantly lacking, limiting the ability of clinical care planning. We recently showed that cortical atrophy in the frontoparietal control network (FPN) at baseline predicts the conversion to dementia in patients with Primary Progressive Aphasia (PPA). Leveraging this methodology, we hypothesized that FPN atrophy would predict progression of dementia in patients diagnosed with bvFTD.MethodWe analyzed data from 48 bvFTD patients (mean age 59.9 years, 20 Female) with very mild or mild dementia from our Frontotemporal Disorders Unit cohort and the Frontotemporal Lobar Degeneration Neuroimaging Initiative. Our primary outcome measure was change in the Clinical Dementia Rating‐FTLD Sum‐of‐Boxes (SoB) at baseline and at least one year later. Each participant underwent baseline MRI scanning for cortical thickness estimates. We ran a Pearson correlation analysis between the annualized change of CDR‐FTLD SoB from baseline to last observation, and baseline cortical network atrophy (quantified as network‐wise W scores). Vertex‐wise GLM analyses and network‐wise bivariate correlation analyses were also used to assess the relationship between network cortical atrophy and annualized CDR changes.ResultOf the 7 networks investigated, only FPN atrophy predicted annualized change in CDR‐FTLD SoB scores (r = ‐0.31, p = 0.03). That is, in bvFTD patients at the very mild/mild dementia stage, the greater the baseline FPN atrophy, the more rapid the clinical decline. Vertex‐wise GLM maps did not show that atrophy across the entire FPN predicted clinical decline. Rather, baseline atrophy in the dorsal precuneus and supramarginal gyrus nodes of the FPN was most predictive of clinical disease progression.ConclusionCortical atrophy in the FPN, and particularly in posterior regions of this network, is predictive of the rate of clinical decline in bvFTD patients, possibly due to the critical roles this network serves in executive function and affective regulation. This work could promote the use of structural imaging biomarkers to guide prognostication for bvFTD patients and their families, and to inform the design of clinical trials.

Visualizing Braak stages with deformation‐based morphometry in super‐sampled MRI

AbstractBackgroundUnlike MRI data, histological data collected post‐mortem can’t be used to study the longitudinal formation of neurofibrillary tangles (NFT) and corresponding brain changes over time for individuals. Although structural MRI offers the possibility of non‐invasive longitudinal antemortem imaging, its resolution is a limiting factor. Using image processing and super‐sampling techniques, we examined the possibility of employing structural MRI to observe the NFT footprints in the brain.MethodData included baseline MRI scans of 1473 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset including ADNI1, 2, and GO. Voxel size was super‐sampled to 0.5×0.5×0.5mm (Manjón et al. 2010) before non‐linear registration to an ADNI‐based unbiased symmetric MRI template. The resulting deformation fields were used to compute the Jacobian determinant map for each subject as a proxy for local volume. For each subject, the sex‐ and age‐corrected z‐scored Jacobian maps were then calculated and averaged for each diagnostic group: normal subjects(CN), early MCI, late MCI, and AD. The average map for CN group was subtracted from the other average maps to show the AD‐stage differences.ResultThe Braak tau staging pattern (Braak & Braak, 1995) is seen in average Jacobian maps as the disease progresses. Subjects in the MCI groups showed on average more pronounced neurodegeneration in the transentorhinal and entorhinal region (Braak Stages 1‐2), followed by degeneration in the hippocampus (Stages 3‐4). Later on, this neurodegeneration progresses toward the neocortex (Stages 5‐6). Figure 1 illustrates these results: A) the template, B)EMCI vs CN, C) LMCI vs EMCI, D) LMCI vs CN, E) AD vs CN. Red color shows an increase and blue indicates a decrease in local volume.ConclusionUsing novel image processing techniques, we were able to verify the staging of AD‐related neurofibrillary pathology progression in MRI data. This shows that structural MRI data, although limited in resolution, can still offer in‐depth insight into the brain antemortem which will in return allow the longitudinal and possible lifespan studies with an accuracy close to histological data.

Exploring gray matter volume atrophy associations with hearing in the UK Biobank

AbstractBackgroundHearing impairment was recently recognized as a modifiable risk factor for dementia. Theories to explain this relationship propose that hearing impairment results in reduced sensory input across the brain, which negatively affects brain structure. Therefore, large exploratory studies are needed to examine potential relationships between hearing and brain volume.Method2,000 participants (age = 63±7 years, 50% female) from the UK Biobank were include in this study. Voxelwise multiple regression models examined the association between hearing and baseline MRI gray matter volume. Hearing was assessed using a speech‐in‐noise task, with positive scores reflecting poorer hearing. Interactions between hearing and sex on brain volume were also explored. Covariates included age, sex (except in model with sex interaction), socioeconomic status, and total intracranial volume. Given the exploratory aim of the analysis, a threshold of p<0.001 was used.ResultThe multiple regression model results showed that poorer hearing is associated with lower gray matter volume in bilateral temporal auditory regions (Heschl’s gyrus, superior temporal gyrus) and left amygdala. While hearing scores did not significantly differ by sex, there were significant hearing‐by‐sex interactions. In women, poorer hearing was associated with lower volume in bilateral auditory regions. In men, poorer hearing was associated with lower volume in right hippocampus and higher volume in posterior cingulate cortex.ConclusionThis study sought to address a major gap in the current literature and explored voxelwise associations between hearing and brain volume in a large sample. The results show that poorer hearing is associated with lower brain volume in lateral and medial temporal regions, which differed by sex. Poorer hearing in women was associated with lower volume in auditory regions, while in men, poorer hearing was associated with lower volume in regions similarly affected by Alzheimer’s disease and dementia. Together, these data provide support for a potential mechanistic explanation for the association between hearing loss and dementia through increased brain atrophy.

Breast MRI radiomics and machine learning radiomics-based predictions of response to neoadjuvant chemotherapy - how are they affected by variations in tumour delineation?

Manual delineation of volumes of interest (VOIs) by experts is considered the gold-standard method in radiomics analysis. However, it suffers from inter- and intra-operator variability. A quantitative assessment of the impact of variations in these delineations on the performance of the radiomics predictors is required to develop robust radiomics based prediction models. In this study, we developed radiomics models for the prediction of pathological complete response to neoadjuvant chemotherapy in patients with two different breast cancer subtypes based on contrast-enhanced magnetic resonance imaging acquired prior to treatment (baseline MRI scans). Different mathematical operations such as erosion, smoothing, dilation, randomization, and ellipse fitting were applied to the original VOIs delineated by experts to simulate variations of segmentation masks. The effects of such VOI modifications on various steps of the radiomics workflow, including feature extraction, feature selection, and prediction performance, were evaluated. Using manual tumour VOIs and radiomics features extracted from baseline MRI scans, an AUC of up to 0.96 and 0.89 was achieved for human epidermal growth receptor 2 positive and triple-negative breast cancer, respectively. For smoothing and erosion, VOIs yielded the highest number of robust features and the best prediction performance, while ellipse fitting and dilation lead to the lowest robustness and prediction performance for both breast cancer subtypes. At most 28% of the selected features were similar to manual VOIs when different VOI delineation data were used. Differences in VOI delineation affects different steps of radiomics analysis, and their quantification is therefore important for development of standardized radiomics research.

Incremental value of volumetric multiparametric MRI over Fudan score for prognosis of unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy

BackgroundIndividualized patient care requires prognostic models customized to a tumor and an individual’s disease profile for reliable survival prediction. MRI has prognostic value for intrahepatic cholangiocarcinoma (ICCA). Existing prognostic models for ICCA exclude imaging-based information about an individual’s tumor that may reflect important aspects of tumor’s biology. Fudan score, a prognostic model applicable to unresectable ICCA, is limited by subjective morphologic imaging parameters. ObjectivesTo assess the prognostic value of baseline volumetric multiparametric MRI in unresectable intrahepatic cholangiocarcinoma (ICCA) treated with systemic chemotherapy and the incremental value of MRI over the Fudan score. MethodsThis retrospective study included 114 ICCA patients treated with systemic chemotherapy between 2007 and 2021 after a baseline MRI. The single largest tumor was volumetrically assessed for anatomic (total tumor volume and diameter) and functional parameters (viable tumor volume, percentage-viable tumor volume, viable tumor burden, and ADC). A derivation cohort of 30 patients was utilized to identify MRI parameters associated with overall survival (OS) using Cox regression analysis. The incremental value of MRI over Fudan score was assessed on an independent sub-cohort of 84 patients using Kaplan-Meier analysis and C-index. Results114 patients (64 years +/- 11; 61 women) were evaluated. Pre-treatment high (>1350x10−6 mm2/sec) ADC was the only independent predictor of OS (HR, 8.07; P < 0.001). Replacing subjective tumor boundary with objective ADC value, and using modified biochemical thresholds increased the prognostic stratification for the risk groups in the modified ADC-Fudan model compared to the original Fudan model (median survival 12 and 4.5 months; P = 0.055; vs. 11 and 3 months; P < 0.001). The modified ADC-Fudan model demonstrated an 11 % improvement over the original Fudan model (c-index: 0.80 vs. 0.69; P = 0.044) for survival prediction. ConclusionsHigh pre-treatment volumetric ADC was associated with unfavorable prognosis in patients with unresectable intrahepatic cholangiocarcinoma treated with systemic chemotherapy. Supplementing the original Fudan model with ADC and modified serum marker thresholds improved the survival prediction performance by 11% in the resulting modified ADC-Fudan model.Clinical Impact: Volumetric MRI could improve the survival prediction among ICCA patients prior to receiving potentially toxic and expensive palliative chemotherapies. This could potentially guide individualized therapy for this patient cohort.

QOL-23. BASELINE TOTAL BRAIN VOLUME PREDICTS FOR POORER QOL AND REDUCED OVERALL SURVIVAL AFTER CRANIAL RADIOTHERAPY IN OLDER PATIENTS WITH GLIOBLASTOMA (GBM): RESULTS FROM THE PROSPECTIVE BRITER STUDY

Abstract GBM incidence peaks in the 7th and 8th decades of life with prognosis worsening with age. Short-course partial brain radiotherapy, +/- chemotherapy, extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy related side effects. BRITER, a prospective multicentre observational trial, recruited patients with newly diagnosed GBM aged ≥ 65 planned for cranial radiotherapy. Baseline MRI scans were analysed for 5 putative markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in QoL. 126 patients were enrolled; mean age 72 years (range 65-83); 67% men, 33% women. 4% had a radiological diagnosis, 19% biopsy and 77% had debulking surgery. 21% received palliative radiotherapy alone (25% 30Gy/6#, 75% 40Gy/15#), 79% received radiotherapy with concurrent TMZ (47% 40Gy/15#, 53% 60Gy/30#). Median OS was 11.3 months. After accounting for age, sex, treatment and baseline MoCA score, there was a significant relationship between baseline CSF:TIV ratio and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV ratio, there was a corresponding decrease in EORTC QLC C30 QoL score by a factor of 1.27 (coefficient -1.27, 95% CI -3.24 to -0.19 p = 0.02). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV ratio was related to risk of non-attendance (OR 1.35, 95% CI 1.01-1.80, p = 0.04). Cox regression models were fitted for time to death in 88 participants who had analysable baseline MRI sequences. Baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19-1.66, p &amp;lt; 0.001). This unique prospective study indicates that baseline imaging parameters can predict the impact of cranial radiotherapy on QoL and OS.

NIMG-18. MULTI-PARAMETRIC MRI AND SPECT ASSESSMENT OF TREATMENT DOSE AND EFFICACY IN RESPECT-GBM FOR RECURRENT GLIOBLASTOMA (RGBM)

Abstract BACKGROUND We have previously shown a dose-dependent association with survival for patients receiving Rhenium-186-nanoliposome (186RNL) for rGBM. This study aim, applying 3D-dosimetry and advanced-MRI features to outcome assessment, was to extend those findings. METHODS SPECT/CT images were acquired at mid-fusion, end-of-infusion, 24-hour, 120-hour, and 192-hour post-186RNL infusion. Baseline MRI was performed within 7days of treatment, at 28d, and every 56d until progression with: T1-3D pre-/post-contrast agent, DSC, DWI. SPECT images were processed using MIM software with treatment volumes corresponding to the 100Gy isodose curve exported as treatment-ROI. Difference (delta T1) between standardized pre-contrast (T1) and post-contrast (T1_C) anatomic images were used to measure tumor volume (IB Rad Tech). Within the tumor, various MRI-derived parameters, such as standardized-relative-cerebral-blood-volume (srCBV), time to maximum (Tmax), time to peak (TTP), were calculated. RESULTS Perfusion analysis(n=8) revealed significant decreases in the mean nrCBF, nrCBV, rCBF, rCBV, and srCBV with dose [nrCBF: -0.25 95% CI -0.37 to -0.14, p=0.005, nrCBV: -0.23 95% CI -0.34 to -0.13, p=0.005, rCBF: -3.5 95% CI -5.37 to -1.63, p=0.01, rCBV: -11.91 95% CI -20.45 to -3.38, p=0.03, srCBV: -0.14 95% CI -0.23 to -0.05, p=0.02], and a significant increase in the mean Tmax [1.88 95% CI 0.58 to 3.17, p=0.03]. The mean volume (n=10) not covered by treatment (-1.59 95% CI -4.81 to 1.63, p=0.36), Tumor volume (-0.76 95% CI -5.23 to 3.72, p=0.75), Treated volume (3.31 95% CI -0.44 to 7.06, p=0.12), and Tumor Volume covered by treatment (0.84 95% CI -1.2 to 2.87, p=0.44) did not vary significantly with dose although may gain significance with a larger data set. CONCLUSION MRI radiographic features proved valuable in assessing treatment efficacy and guiding treatment considerations. Image processing is ongoing, and the complete data set will be presented.

Quantitative T1 brain mapping in early relapsing-remitting multiple sclerosis: longitudinal changes, lesion heterogeneity and disability

ObjectivesTo quantify brain microstructural changes in recently diagnosed relapsing-remitting multiple sclerosis (RRMS) using longitudinal T1 measures, and determine their associations with clinical disability.MethodsSeventy-nine people with recently diagnosed (< 6 months) RRMS were recruited from a single-centre cohort sub-study, and underwent baseline and 1-year brain MRI, including variable flip angle T1 mapping. Median T1 was measured in white matter lesions (WML), normal-appearing white matter (NAWM), cortical/deep grey matter (GM), thalami, basal ganglia and medial temporal regions. Prolonged T1 (≥ 2.00 s) and supramedian T1 (relative to cohort WML values) WML voxel counts were also measured. Longitudinal change was assessed with paired t-tests and compared with Bland-Altman limits of agreement from healthy control test-retest data. Regression analyses determined relationships with Expanded Disability Status Scale (EDSS) score and dichotomised EDSS outcomes (worsening or stable/improving).ResultsSixty-two people with RRMS (mean age 37.2 ± 10.9 [standard deviation], 48 female) and 11 healthy controls (age 44 ± 11, 7 female) contributed data. Prolonged and supramedian T1 WML components increased longitudinally (176 and 463 voxels, respectively; p < .001), and were associated with EDSS score at baseline (p < .05) and follow-up (supramedian: p < .01; prolonged: p < .05). No cohort-wide median T1 changes were found; however, increasing T1 in WML, NAWM, cortical/deep GM, basal ganglia and thalami was positively associated with EDSS worsening (p < .05).ConclusionT1 is sensitive to brain microstructure changes in early RRMS. Prolonged WML T1 components and subtle changes in NAWM and GM structures are associated with disability.Clinical relevance statementMRI T1 brain mapping quantifies disability-associated white matter lesion heterogeneity and subtle microstructural damage in normal-appearing brain parenchyma in recently diagnosed RRMS, and shows promise for early objective disease characterisation and stratification.Key Points• Quantitative T1 mapping detects brain microstructural damage and lesion heterogeneity in recently diagnosed relapsing-remitting multiple sclerosis.• T1 increases in lesions and normal-appearing parenchyma, indicating microstructural damage, are associated with worsening disability.• Brain T1 measures are objective markers of disability-relevant pathology in early multiple sclerosis.Graphical abstract

Clinical and imaging outcomes of 100 patients with cerebrospinal fluid-venous fistulas treated by transvenous embolization

BackgroundCerebrospinal fluid-venous fistulas (CSFVF) are a common cause of spontaneous intracranial hypotension (SIH). Transvenous embolization has emerged as a reliable treatment option. We review the clinical presentation, imaging, and clinical...

A deep learning-based comparative MRI model to detect inflammatory changes in rheumatoid arthritis

Rheumatoid Arthritis (RA) is an autoimmune disease that mainly affects joints in the wrist and hands. It typically results in inflamed and painful joints. MRI is one of the most common imaging modalities to detect and monitor possible inflamed RA-related areas, enabling rheumatologists to treat patients more timely and efficiently. Despite the importance of finding and tracking inflamed areas associated with RA in MRI, there is no previously published work on finding pixel-by-pixel changes related to RA between baseline and follow-up MRIs. Therefore, this paper proposes a hypothesis-free deep learning-based model to discover changes in wrist MRIs on a pixel level to detect changes in inflamed areas related to RA without using prior anatomical information. To do this, a combination of a U-Net-based network and image thresholding was utilised to find pixel-level non-trivial changes between baseline and follow-up MRI images. A wrist MRI dataset including 99 individual pairs of MRI images (each pair constructed of baseline and follow-up images) was used to evaluate the proposed model. Data were collected from patients with clinically suspected arthralgia (CSA), defined as patients at risk of developing RA according to their rheumatologist and already had subclinical inflammation on MRI but could not be diagnosed with RA (yet) since they had not developed clinically detectable arthritis. The obtained results were evaluated using an observer study. The evaluation showed that our proposed model is a promising first step toward developing an automatic model to find RA-related inflammatory changes.

Cervical Vertebral Bone Quality Score Independently Predicts Distal Junctional Kyphosis After Posterior Cervical Fusion.

Posterior cervical fusion is the surgery of choice when fusing long segments of the cervical spine. However, because of the limited presence of this pathology, there is a paucity of data in the literature about the postoperative complications of distal junctional kyphosis (DJK). We aimed to identify and report potential associations between the preoperative cervical vertebral bone quality (C-VBQ) score and the occurrence of DJK after posterior cervical fusion. The authors retrospectively reviewed records of patients who underwent posterior cervical fusion at a single hospital between June 1, 2010, and May 31, 2020. Patient data were screened to include patients who were >18 years old, had baseline MRI, had baseline standing cervical X-ray, had immediate postoperative standing cervical X-ray, and had clinical and radiographic follow-ups of >1 year, including a standing cervical X-ray at least 1 year postoperatively. Univariate analysis was completed between DJK and non-DJK groups, with multivariate regression completed for relevant clinical variables. Simple linear regression was completed to analyze correlation between the C-VBQ score and total degrees of kyphosis angle change. Ninety-three patients were identified, of whom 19 (20.4%) had DJK and 74 (79.6%) did not. The DJK group had a significantly higher C-VBQ score than the non-DJK group (2.97 ± 0.40 vs 2.26 ± 0.46; P < .001). A significant, positive correlation was found between the C-VBQ score and the total degrees of kyphosis angle change (r 2 = 0.26; P < .001). On multivariate analysis, the C-VBQ score independently predicted DJK (odds ratio, 1.46; 95% CI, 1.27-1.67; P < .001). We found that the C-VBQ score was an independent predictive factor of DJK after posterior cervical fusion.

Intrinsic brain functional connectivity predicts treatment-related motor complications in early Parkinson’s disease patients

BackgroundTreatment-related motor complications may develop progressively over the course of Parkinson’s disease (PD).ObjectiveWe investigated intrinsic brain networks functional connectivity (FC) at baseline in a cohort of early PD patients which successively developed treatment-related motor complications over 4 years.MethodsBaseline MRI images of 88 drug-naïve PD patients and 20 healthy controls were analyzed. After the baseline assessments, all PD patients were prescribed with dopaminergic treatment and yearly clinically re-assessed. At the 4-year follow-up, 36 patients have developed treatment-related motor complications (PD-Compl) whereas 52 had not (PD-no-Compl). Single-subject and group-level independent component analyses were used to investigate FC changes within the major large-scale resting-state networks at baseline. A multivariate Cox regression model was used to explore baseline predictors of treatment-related motor complications at 4-year follow-up.ResultsAt baseline, an increased FC in the right middle frontal gyrus within the frontoparietal network as well as a decreased connectivity in the left cuneus within the default-mode network were detected in PD-Compl compared with PD-no-Compl. PD-Compl patients showed a preserved sensorimotor FC compared to controls. FC differences were found to be independent predictors of treatment-related motor complications over time.ConclusionOur findings demonstrated that specific FC differences may characterize drug-naïve PD patients more prone to develop treatment-related complications. These findings may reflect the presence of an intrinsic vulnerability across frontal and prefrontal circuits, which may be potentially targeted as a future biomarker in clinical trials.

Longitudinal associations of serum biomarkers with early cognitive, amyloid and grey matter changes.

Blood-based biomarkers have been extensively evaluated for their diagnostic potential in Alzheimer's disease. However, their relative prognostic and monitoring capabilities for cognitive decline, amyloid-β (Aβ) accumulation and grey matter loss in cognitively unimpaired elderly require further investigation over extended time periods. This prospective cohort study in cognitively unimpaired elderly [n = 185, mean age (range) = 69 (53-84) years, 48% female] examined the prognostic and monitoring capabilities of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), Aβ1-42/Aβ1-40 and phosphorylated tau (pTau)181 through their quantification in serum. All participants underwent baseline Aβ-PET, MRI and blood sampling as well as 2-yearly cognitive testing. A subset additionally underwent Aβ-PET (n = 109), MRI (n = 106) and blood sampling (n = 110) during follow-up [median time interval (range) = 6.1 (1.3-11.0) years]. Matching plasma measurements were available for Aβ1-42/Aβ1-40 and pTau181 (both n = 140). Linear mixed-effects models showed that high serum GFAP and NfL predicted future cognitive decline in memory (βGFAP×Time = -0.021, PFDR = 0.007 and βNfL×Time = -0.031, PFDR = 0.002) and language (βGFAP×Time = -0.021, PFDR = 0.002 and βNfL×Time = -0.018, PFDR = 0.03) domains. Low serum Aβ1-42/Aβ1-40 equally but independently predicted memory decline (βAβ1-42/Aβ1-40×Time = -0.024, PFDR = 0.02). Whole-brain voxelwise analyses revealed that low Aβ1-42/Aβ1-40 predicted Aβ accumulation within the precuneus and frontal regions, high GFAP and NfL predicted grey matter loss within hippocampal regions and low Aβ1-42/Aβ1-40 predicted grey matter loss in lateral temporal regions. Serum GFAP, NfL and pTau181 increased over time, while Aβ1-42/Aβ1-40 decreased only in Aβ-PET-negative elderly. NfL increases associated with declining memory (βNfLchange×Time = -0.030, PFDR = 0.006) and language (βNfLchange×Time = -0.021, PFDR = 0.02) function and serum Aβ1-42/Aβ1-40 decreases associated with declining language function (βAβ1-42/Aβ1-40×Time = -0.020, PFDR = 0.04). GFAP increases associated with Aβ accumulation within the precuneus and NfL increases associated with grey matter loss. Baseline and longitudinal serum pTau181 only associated with Aβ accumulation in restricted occipital regions. In head-to-head comparisons, serum outperformed plasma Aβ1-42/Aβ1-40 (ΔAUC = 0.10, PDeLong, FDR = 0.04), while both plasma and serum pTau181 demonstrated poor performance to detect asymptomatic Aβ-PET positivity (AUC = 0.55 and 0.63, respectively). However, when measured with a more phospho-specific assay, plasma pTau181 detected Aβ-positivity with high performance (AUC = 0.82, PDeLong, FDR < 0.007). In conclusion, serum GFAP, NfL and Aβ1-42/Aβ1-40 are valuable prognostic and/or monitoring tools in asymptomatic stages providing complementary information in a time- and pathology-dependent manner.

MD Anderson Phase III Randomized Preoperative Stereotactic Radiosurgery (SRS) vs. Postoperative SRS for Brain Metastases Trial

Postoperative stereotactic radiation therapy/radiosurgery (SRT/SRS) is being evaluated in comparison to Preoperative SRT for brain metastases (mets) in a limited number of prospective clinical trials. Our objective is to address the significant knowledge gap concerning the logistics of preoperative SRT in comparison to postoperative SRT in a randomized controlled study. Patients with brain mets with at least 1 surgically operable met were randomized (1:1) to Preop vs Postop SRT. In this abstract, we present non-primary endpoint data on the trial concept and logistics of treatment for this data safety monitoring board reviewed study. Patients enrolled had 1-2 lesions resected and <15 lesions treated at time of SRT to best reflect the standard population that receive SRT and surgery at our institution. From 12/2018 to 12/2022, 99 patients with 1-2 operable brain mets were enrolled and randomized to Preop (n = 49) or Postop (n = 50) SRT. Males represented 56% of the cohort compared to females, and <25% were age 18-49 years, while 27%, 29, and 19% respectively were 50-59, 60-69, and > = 70. The most frequent histologies enrolled were lung (29%), renal cell (15%), melanoma (14%), and breast (11%) cancers. The majority of patients (83%) had 1-4 brain mets on their baseline MRI and 91% subsequently had a single lesion resected. Seventy-nine patients completed both SRT and surgery, while 9% received no therapy due to drop out before study therapy initiation. Among patients receiving both therapies in the combined cohort, 68% received a non-invasive stereotactic radiosurgery instrument to the randomized cavity lesion compared to 32% receiving LINAC based SRT. Treatment of the lesion or cavity with single fraction SRT was 51% in the Preop arm vs 31% in the Postop arm. Multi-fraction (3-5 SRT) was 67% in the Postop cohort in contrast to 47% in the Preop cohort. Time from randomization to RT was 5.6 days and 33.7 days in the Preop and Postop cohorts respectively, and for surgery was 10.2 days vs 12.9 days in the Postop vs Preop cohorts. The average time from RT to surgery was 7.3 days in the Preop arm and 23.5 days in the Postop arm (to allow for incisional healing time). In one of the early initiated randomized prospective cohorts of Preop vs Postop SRT, we demonstrated logistical feasibility with an efficient clinical trial workflow for study treatment. Differences in Preop vs Postop logistics reflect clinical practice differences in time-to-treatment. Therapy with various modalities reflected real-world practice and possibly provider preferences in technique when addressing the nature of delineating cavities and changes in cavity volume with regard to fractionation. Independent of the primary outcomes, our data provides insights in the practical management of patients receiving these two modalities of therapy, and further data at the completion of trial will address relevant primary outcomes.

Role of Stereotactic Body Radiation Therapy in Portal Vein Tumor Thrombosis in Hepatocellular Carcinoma: A Prospective Single Institute Experience

Patients diagnosed with Hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombosis (PVTT) have a limited number of treatment options available and are associated with an overall poor prognosis. With the recent developments in the field of radiation therapy, the role of radiotherapy particularly Stereotactic Body radiotherapy (SBRT) has increased as a loco-regional therapy for HCC. This study was planned to evaluate the role of SBRT in Locally advanced HCC complicated with PVTT and its role as loco-regional therapy. We conducted a prospective study that included patients diagnosed with HCC complicated with PVTT Child-Turcotte Pugh (CTP) Class A/B with a maximum score of 7, diagnosed on triple phase Contrast-Enhanced - MRI unsuitable for other ablative procedures. Patients with Bilirubin levels > 4 mg/dl, active Hepatitis, CTP score >7, normal liver volume <700cc or history of prior radiotherapy were excluded from the study. Patients underwent a contrast enhanced 4D-CT simulation with abdominal compression and were planned for SBRT using VMAT technique. Patients were followed-up as per Institute protocol. CECT or MRI for a radiological response was done for response assessment using mRECIST criteria version 1.1. A baseline MRI was done at one-month post-SBRT to understand any RT changes in the liver and to differentiate from tumor progression during the response assessment at three months. A total of 22 patients with HCC were recruited and received SBRT to PVTT, with a dosage between 30-42 Gy over 6 fractions treated on alternate days. Patients were assessed post-treatment with triphasic CE-MRI every 3 months as per institute protocol. Five patients had achieved Complete response in form of Portal vein recanalization. Three patients had Partial response to the treatment. Seven patients maintained stable disease status whereas six patients had disease progression during the entire course of treatment. The response rate (CR+PR) to treatment was 36.3% at the time of analysis. The Overall Response rate (CR+PR+SD) was 69%. No grade 3 or 4 toxicities were observed and treatment was tolerated well by patients. Kaplan-Meier method was applied to calculate the survival probability at various follow-up intervals. The median time for overall survival was 25 months ((95% CI: 15-35). Out of the 22 subjects included in the study, 6 patients died. There was a 78% survival probability at 12 months and a 68% survival probability at 18 months of follow-up. This prospective single-arm study demonstrated the vital role of SBRT in the treatment of Hepatocellular carcinoma with Portal vein tumor thrombosis and its efficacy in terms of achieving excellent local control with relatively lesser toxicities compared with existing treatment modalities. Patients have shown benefit post-treatment in terms of thrombus reduction and restoration of Portal vein flow making them suitable for further treatment like Resection or TACE.

Correlation between synthetic MRI relaxometry and apparent diffusion coefficient in breast cancer subtypes with different neoadjuvant therapy response

BackgroundTo evaluate the correlation between synthetic MRI (syMRI) relaxometry and apparent diffusion coefficient (ADC) maps in different breast cancer subtypes and treatment response subgroups.MethodsTwo hundred sixty-three neoadjuvant therapy (NAT)-treated breast cancer patients with baseline MRI were enrolled. Tumor annotations were obtained by drawing regions of interest (ROIs) along the lesion on T1/T2/PD and ADC maps respectively. Histogram features from T1/T2/PD and ADC maps were respectively calculated, and the correlation between each pair of identical features was analyzed. Meanwhile, features between different NAT treatment response groups were compared, and their discriminatory power was evaluated.ResultsAmong all patients, 20 out of 27 pairs of features weakly correlated (r = – 0.13–0.30). For triple-negative breast cancer (TNBC), features from PD map in the pathological complete response (pCR) group (r = 0.60–0.86) showed higher correlation with ADC than that of the non-pCR group (r = 0.30–0.43), and the mean from the ADC and PD maps in the pCR group strongly correlated (r = 0.86). For HER2-positive, few correlations were found both in the pCR and non-pCR groups. For luminal HER2-negative, T2 map correlated more with ADC than T1 and PD maps. Significant differences were seen in T2 low percentiles and median in the luminal-HER2 negative subtype, yielding moderate AUCs (0.68/0.72/0.71).ConclusionsThe relationship between ADC and PD maps in TNBC may indicate different NAT responses. The no-to-weak correlation between the ADC and syMRI suggests their complementary roles in tumor microenvironment evaluation.Critical relevance statementThe relationship between ADC and PD maps in TNBC may indicate different NAT responses, and the no-to-weak correlation between the ADC and syMRI suggests their complementary roles in tumor microenvironment evaluation.Key points• The relationship between ADC and PD in TNBC indicates different NAT responses.• The no-to-weak correlations between ADC and syMRI complementarily evaluate tumor microenvironment.• T2 low percentiles and median predict NAT response in luminal-HER2-negative subtype.Graphical

Prognostic value of baseline MRI features in patients treated with thermal ablation for hepatocellular carcinoma

PurposeTo investigate prognostic value of baseline MRI features for time-to-recurrence (TTR) and local recurrence in patients with early hepatocellular carcinoma (HCC). MethodBaseline and follow-up images of 88 patients treated with thermal ablation followed by adjuvant sorafenib or matching placebo due to HCC within the phase II prospective randomized trial (SORAMIC) were included. Baseline MRI images were evaluated in terms of atypical enhancement (lack of wash-in or wash-out), lesion diameter, tumor capsule, peritumoral enhancement on arterial phase, intratumoral fat, irregular margin, satellite lesions, and peritumoral hypointensity on hepatobiliary phase. Prognostic value of these features for TTR and local recurrence were assessed with univariable and multivariable Cox proportional hazard models. ResultsRecurrence at any location was diagnosed during follow-up in 30 patients, and the median TTR was 16.4 (95% CI, 15 – NA) months. The presence of more than one lesion (p = 0.028) and peritumoral hypointensity on hepatobiliary phase images (p = 0.012) at baseline were significantly associated with shorter TTR in univariable analysis. AFP > 15 mg/dL (p = 0.084), and history of cirrhosis (p = 0.099) were marginally non-significant. Peritumoral hypointensity on hepatobiliary phase images was the only significant risk factor for recurrence in multivariable analysis (p = 0.003).Local recurrence (adjacent to thermal scar) was diagnosed in eleven (8.3%) out of 132 lesions that underwent thermal ablation. The only significant risk factor for local recurrence was a lesion diameter larger than 3 cm (22.2% vs. 4.5%, p = 0.007). ConclusionsPeritumoral hypointensity on hepatobiliary phase can serve as imaging biomarker to identify increased recurrence risk in patients undergoing thermal ablation for early-stage HCC.

Fractal dimension of the cortical gray matter outweighs other brain MRI features as a predictor of transition to dementia in patients with mild cognitive impairment and leukoaraiosis.

The relative contribution of changes in the cerebral white matter (WM) and cortical gray matter (GM) to the transition to dementia in patients with mild cognitive impairment (MCI) is not yet established. In this longitudinal study, we aimed to analyze MRI features that may predict the transition to dementia in patients with MCI and T2 hyperintensities in the cerebral WM, also known as leukoaraiosis. Sixty-four participants with MCI and moderate to severe leukoaraiosis underwent baseline MRI examinations and annual neuropsychological testing over a 2 year period. The diagnosis of dementia was based on established criteria. We evaluated demographic, neuropsychological, and several MRI features at baseline as predictors of the clinical transition. The MRI features included visually assessed MRI features, such as the number of lacunes, microbleeds, and dilated perivascular spaces, and quantitative MRI features, such as volumes of the cortical GM, hippocampus, T2 hyperintensities, and diffusion indices of the cerebral WM. Additionally, we examined advanced quantitative features such as the fractal dimension (FD) of cortical GM and WM, which represents an index of tissue structural complexity derived from 3D-T1 weighted images. To assess the prediction of transition to dementia, we employed an XGBoost-based machine learning system using SHapley Additive exPlanations (SHAP) values to provide explainability to the machine learning model. After 2 years, 18 (28.1%) participants had transitioned from MCI to dementia. The area under the receiving operator characteristic curve was 0.69 (0.53, 0.85) [mean (90% confidence interval)]. The cortical GM-FD emerged as the top-ranking predictive feature of transition. Furthermore, aggregated quantitative neuroimaging features outperformed visually assessed MRI features in predicting conversion to dementia. Our findings confirm the complementary roles of cortical GM and WM changes as underlying factors in the development of dementia in subjects with MCI and leukoaraiosis. FD appears to be a biomarker potentially more sensitive than other brain features.

Association of MRI leptomeningeal enhancement with disability worsening in progressive multiple sclerosis: A clinical and post-mortem study

Background: Leptomeningeal enhancement (LME) has been described as a biomarker of meningeal inflammation in multiple sclerosis (MS). Objective: The aim of this study was to (1) assess if LME is predictive of disability worsening in progressive MS (pMS) patients and (2) investigate the pathological substrates of LME in an independent post-mortem MS series. Methods: In total, 115 pMS patients were imaged yearly with 1.5T MRI, using post-contrast CUBE 3D FLAIR for LME detection. Endpoint: to identify the baseline variables predictive of confirmed disability worsening (CDW) at 24 months follow-up. Post-mortem, inflammation, and structural changes of the leptomeninges were assessed in 12 MS/8 control brains. Results: LME (27% of patients at baseline) was associated with higher EDSS and lower brain volume (nBV). LME was unchanged in most patients over follow-up. LME at baseline MRI was independently associated with higher risk of 24 months CDW (HR 3.05, 95% CI 1.36–6.84, p = 0.007) in a Cox regression, including age, nBV, T2 lesion volume, high-efficacy treatments, and MRI disease activity. Post-mortem, focal structural changes (fibrosis) of the leptomeninges were observed in MS, usually associated with inflammation (Kendall’s Tau 0.315, p < 0.0001). Conclusions: LME is frequently detected in pMS patients using 1.5T MRI and is independently predictive of disability progression. LME could result from both focal leptomeningeal post-inflammatory fibrosis and inflammation.

Prognostic significance of MRI-defined sarcopenia in patients with nasopharyngeal carcinoma: A propensity score matched analysis of real-world data

Background and purposeImage-defined sarcopenia is linked to increased mortality among patients with cancer. Nevertheless, its effect on patients with nasopharyngeal carcinoma (NPC) is incompletely established. This study’s aim was to investigate the prognostic significance of MRI-defined sarcopenia on the survival of patients undergoing concurrent chemoradiotherapy (CCRT) ± inducing chemotherapy (IC) for NPC treatment. Methods1,307 patients with stage II-IVa NPC were included in this retrospective study. Sarcopenia was defined using skeletal muscle index (SMI) determined through baseline MRI at the C3 level. The association of sarcopenia with overall survival (OS) and progression-free survival (PFS) was assessed by Cox regression models using 1:1 propensity score matching (PSM) analysis. We also conducted a stratification analysis using BMI and treatment strategies. ResultsSarcopenia was an independent risk factor for both OS and PFS (all P < 0.05). However, BMI was not substantially linked to OS and PFS (all P > 0.05). Sarcopenic patients showed lower rates of OS (HR = 2.00, 95% CI: 1.54–2.60, P < 0.001) and PFS (HR = 1.67, 95% CI: 1.35–2.07, P < 0.001) in contrast with nonsarcopenic patients. According to stratification analysis, being overweight was linked to a protective effect in nonsarcopenic patients only. Sarcopenic patients showed similar OS and PFS regardless of the treatment modality. ConclusionsSarcopenia is underrecognized in NPC patients. Measurement of sarcopenia using routine MRI scans in NPC patients provided significant prognostic information, outperforming BMI. Patients with sarcopenia failed to benefit from an additional IC regimen.