Tracking transplanted bone marrow stem cells and their effects in the rat MCAO stroke model.

In this study, rat bone marrow stromal stem cells (BMSCs) were tracked after IV administration to rats with experimental stroke caused by middle cerebral artery occlusion (MCAO). In addition, the effects of BMSC treatment on blood cell composition, brain glia and sensorimotor behavior was studied and compared to that which occurred spontaneously during the normal recovery process after stroke. We found that the vast majority of radiolabeled or fluorescently labeled BMSCs traveled to and remained in peripheral organs (lungs, spleen, liver) 3 days after IV injection in the MCAO rat. Once in the circulation, BMSCs also produced rapid alterations in host blood cell composition, increasing both neutrophil and total white blood cell count by 6 hours post-injection. In contrast, few injected BMSCs traveled to the brain and almost none endured there long term. Nonetheless, BMSC treatment produced dramatic changes in the number and activation of brain astroglia and microglia, particularly in the region of the infarct. These cellular changes were correlated with a marked improvement in performance on tests of sensory and motor function as compared to the partial recovery of function seen in PBS-injected control rats. We conclude that the notable recovery in function observed after systemic administration of BMSCs to MCAO rats is likely due to the cellular changes in blood and/or brain cell number, activation state and their cytokine/growth factor products

Multi-dimension unified Swin Transformer for 3D Lesion Segmentation in Multiple Anatomical Locations

In oncology research, accurate 3D segmentation of lesions from CT scans is essential for the modeling of lesion growth kinetics. However, following the RECIST criteria, radiologists routinely only delineate each lesion on the axial slice showing the largest transverse area, and delineate a small number of lesions in 3D for research purposes. As a result, we have plenty of unlabeled 3D volumes and labeled 2D images, and scarce labeled 3D volumes, which makes training a deep-learning 3D segmentation model a challenging task. In this work, we propose a novel model, denoted a multi-dimension unified Swin transformer (MDU-ST), for 3D lesion segmentation. The MDU-ST consists of a Shifted-window transformer (Swin-transformer) encoder and a convolutional neural network (CNN) decoder, allowing it to adapt to 2D and 3D inputs and learn the corresponding semantic information in the same encoder. Based on this model, we introduce a three-stage framework: 1) leveraging large amount of unlabeled 3D lesion volumes through self-supervised pretext tasks to learn the underlying pattern of lesion anatomy in the Swin-transformer encoder; 2) fine-tune the Swin-transformer encoder to perform 2D lesion segmentation with 2D RECIST slices to learn slice-level segmentation information; 3) further fine-tune the Swin-transformer encoder to perform 3D lesion segmentation with labeled 3D volumes. The network's performance is evaluated by the Dice similarity coefficient (DSC) and Hausdorff distance (HD) using an internal 3D lesion dataset with 593 lesions extracted from multiple anatomical locations. The proposed MDU-ST demonstrates significant improvement over the competing models. The proposed method can be used to conduct automated 3D lesion segmentation to assist radiomics and tumor growth modeling studies. This paper has been accepted by the IEEE International Symposium on Biomedical Imaging (ISBI) 2023

Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials

A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials. The minimum recommended sequences include: (i) parameter-matched precontrast and postcontrast inversion recovery-prepared, isotropic 3D T1-weighted gradient-recalled echo; (ii) axial 2D T2-weighted turbo spin-echo acquired after contrast injection and before postcontrast 3D T1-weighted images to control timing of images after contrast administration; (iii) precontrast, axial 2D T2-weighted fluid-attenuated inversion recovery; and (iv) precontrast, axial 2D, 3-directional diffusion-weighted images. Recommended ranges of sequence parameters are provided for both 1.5 T and 3 T MR system

Improved Outcome Prediction Using CT Angiography in Addition to Standard Ischemic Stroke Assessment: Results from the STOPStroke Study

Purpose: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS.2. Strokes were classified as ‘‘major’ ’ by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was#7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores.10. Results: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p,0.0001). Combining NIHSS with BASIS was highly predictive: 77.6 % (114/147) classified as NIHSS.10/BASIS+ had poor outcomes, versus 21.5 % (77/358) with NIHSS#10/BASIS2 (p,0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95 % CI: 7.9 to 20.0

3D Segmentation of Necrotic Lung Lesions in CT Images Using Self-Supervised Contrastive Learning

Deep convolutional neural networks (CNN) are often trained on 2D annotations created by radiologists following RECIST guidelines to segment lesions in 3D medical images. Three-dimensional segmentation is conducted by segmenting each lesion slice-by-slice on the axial direction and stacking the 2D segmentation masks into 3D. However, the performance of such models is inherently biased by the appearance of most of the lesions in the training dataset. Herein we propose an approach to generate accurate 3D segmentations of underrepresented necrotic lung lesions. Our proposed approach applies two novel augmentation techniques for contrastive learning pretraining: dependency augmentation that captures inter-slice dependencies, and distance transform-based mask-out augmentation imitating necrotic lesions. In dependency augmentation, cosine similarity within RECIST bounding box is applied to construct positive pairs from 2D image slices of the same lesion in the current 3D volume and across longitudinal scans. We further compared contrastive learning architectures, Momentum Contrast (MoCo) and Bootstrap Your Own Latent (BYOL), based upon two internal 3D testing sets, one with regular lung lesions and the other with necrotic lung lesions, and a public 3D DeepLesion lung lesion testing set. MoCo with both proposed augmentations demonstrated the best performance among all methods that were compared. Specifically, it 1) improved Dice similarity coefficient (DSC) by 8.42% over baseline model trained from scratch and 2.40% over ImageNet pretrained model on the 3D necrotic lung lesion set; 2) achieved better segmentation performance on necrotic lesions with 10% of labeled data for supervised fine-tuning compared with the baseline model trained with all labels from scratch

Analysis of blood composition before and after MCAO and rat BMSC treatment.

<p>Blood was collected from the tail vein before and 24 hr after MCAO and 6 and 24 hours after IV injection of BMSCs and quantitatively analyzed for counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and large unstained cells (LUC) by Bioreliance (Rockville, MD). (N = 3) *p<0.05 and **p<0.01.</p

Correlation of BMSC treatment with a significant improvement in behavior over time.

<p>All behavioral assessments as described in Fig. legend 2. Panel A. Sensorimotor behavior as assessed on the mNSS scale 1 or 4 weeks after PBS or BMSC treatment (compared to mNSS score at 1 day post-MCAO set to 100%). Panel B. Climbing ability as assessed on the forelimb asymmetry test at 1, 2, 3 and 4 weeks after PBS or BMSC treatment. When compared to pre-MCAO performance on day 0, PBS groups wer significantly different at all treatment times while those treated with BMSCs differed at 1 and 2 weeks post-treatment but normalized towards control at later time points. Importantly, forelimb asymmetry was significantly different (p<0.001) between BMSC and PBS treatment groups at all 4 treatment times. Panel C. Corner test evaluated at 1 day, 1 and 4 weeks after PBS or BMSC treatment (compared to pre-MCAO performance on day 0). N = 6, *p<0.01 and **p<0.001.</p

Analysis of infarct severity and extent on PET/CT imaging in representative sham and MCAO brains.

<p>A. Coronal view of a sham-operated animal showing normal symmetrical glucose uptake. B. One day post-MCAO, there is decreased uptake on the side of the infarct. C. Axial and coronal images showing placement of 2 mm thick ovoid regions of interest (ROIs) [symmetrical across the midline, arbitrary colors] across the cerebral hemispheres. D. Mean standardized uptake value (SUV) ratios (infarcted to contralateral side ROI) are plotted against slice position comparing infarcted and sham-operated control rat shown in A–C. The severity of the infarct is reflected both by the number of slices affected, and the degree to which activity is suppressed (relative to normal) in each slice. Over 4 weeks, there was a modest spontaneous improvement in FDG uptake, which correlated with the improvement seen in mNSS scores from 6 to 4 (not shown). Imaging was repeated for 3 sham-lesioned and 3 MCAO lesioned rats.</p