Seyed-Parsa Hojjat

Effect of Collaterals on Clinical Presentation, Baseline Imaging, Complications, and Outcome in Acute Stroke

BACKGROUND AND PURPOSE: Good CTA collaterals independently predict good outcome in acute ischemic stroke. Our aim was to evaluate the role of collateral circulation and its added benefit over CTP-derived total ischemic volume as a predictor of baseline NIHSS score, total ischemic volume, hemorrhagic transformation, final infarct size, and a modified Rankin Scale score >2. MATERIALS AND METHODS: This was a retrospective study of 395 patients with stroke dichotomized by recanalization (recanalization positive/recanalization negative) and collateral status. Clot burden score was quantified on baseline CTA. Total ischemic volumes were derived from thresholded CTP maps. Final infarct size was assessed on follow-up CT/MRI. We performed uni-/multivariate analyses for each outcome, adjusting for rtPA status, using general linear (continuous variables) and logistic (binary variables) regression. Model comparison with collateral score and total ischemic volume was performed using the F or likelihood ratio test. RESULTS: Collateral presence independently and inversely predicted all outcomes except hemorrhagic transformation in patients who were recanalization negative and mRS >2 in patients who were recanalization positive. The greatest collateral benefit occurred in patients who were recanalization negative, contributing 16.5% and 19.2% of the variability for final infarct size and mRS >2. The collateral score model is superior to the total ischemic volume for mRS >2 prediction, but a combination of total ischemic volume and collateral score is superior for mRS >2 and final infarct prediction (24% and 28% variability, respectively). In patients who were recanalization positive, a model including collateral score and total ischemic volume was superior to that of total ischemic volume for hemorrhagic transformation and final infarct prediction but was muted compared with patients who were recanalization negative (11.3% and 16.9% variability). CONCLUSIONS: Collateral circulation is an independent predictor of all outcomes, but the magnitude of significance varies, greater in patients who were recanalization negative versus recanalization positive. Total ischemic volume assessment is complementary to collateral score in many cases.

Quantification of the effect of osteolytic metastases on bone strain within whole vertebrae using image registration.

The vertebral column is the most frequent site of metastatic involvement of the skeleton with up to 1/3 of all cancer patients developing spinal metastases. Longer survival times for patients, particularly secondary to breast cancer, have increased the need for better understanding the impact of skeletal metastases on structural stability. This study aims to apply image registration to calculate strain distributions in metastatically involved rodent vertebrae utilizing µCT imaging. Osteolytic vertebral lesions were developed in five rnu/rnu rats 2–3 weeks post intracardiac injection with MT‐1 human breast cancer cells. An image registration algorithm was used to calculate and compare strain fields due to axial compressive loading in metastatically involved and control vertebrae. Tumor‐bearing vertebrae had greatly increased compressive strains, double the magnitude of strain compared to control vertebrae (p = 0.01). Qualitatively strain concentrated within the growth plates in both tumor bearing and control vertebrae. Most interesting was the presence of strain concentrations at the dorsal wall in metastatically involved vertebrae, suggesting structural instability. Strain distributions, quantified by image registration were consistent with known consequences of lytic involvement. Metastatically involved vertebrae had greater strain magnitude than control vertebrae. Strain concentrations at the dorsal wall in only the metastatic vertebrae, were consistent with higher incidence of burst fracture secondary to this pathology. Future use of image registration of whole vertebrae will allow focused examination of the efficacy of targeted and systemic treatments in reducing strains and the related risk of fracture in pathologic bones under simple and complex loading.

Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients.

Background: Cognitive impairment affects 40%–68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. Methods: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. Results: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale–Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). Conclusion: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences.

Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients

Purpose: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences.

Automated quantitative microstructural analysis of metastatically involved vertebrae: effects of stereologic model and spatial resolution

SUMMARY OF BACKGROUND DATA Preclinical models of spinal metastases allow for the application of micro-image based structural assessments, however, large data sets resulting from high resolution scanning motivate a need for robust automated analysis tools. Accurate assessment of changes in vertebral architecture, however, may depend both on the resolution of images acquired and the models used to represent the structural data. OBJECTIVE To apply a recently developed automated μCT based analysis tool to quantify the effect of diffuse metastatic disease on rat vertebral architecture at multiple resolutions. It was hypothesized that automated methods could accurately quantify differences in vertebral microstructure and that diffuse metastatic disease could be shown to have significant negative architectural effects on trabecular bone independent of stereologic model and resolution. METHODS μCT images acquired at 14 μm(3) of healthy and metastatically involved whole lumbar rat vertebrae were analyzed at high, medium and low (8.725, 17.45, and 34.9 μm(3)) resolutions using an automated algorithm to yield micro-structural measures of the trabecular centrum and cortical shell. The images analyzed at different resolutions were obtained via up/downsampling of the acquired image data. Trabecular thickness was evaluated with the Parfitt and Hildebrand models, and anisotropy was evaluated through calculation of mean intercept length. RESULTS Significant differences in microstructural parameters measured in comparing healthy and metastatically involved vertebrae were affected by resolution, however, relative anisotropy was maintained. The Parfitt and Hilderbrand models yielded similar structural differences between healthy and metastatic vertebrae, however, the Hildebrand model was limited due to segmentation accuracy required for its automated application. CONCLUSIONS Differences in microstructural parameters generated through automated analysis at high resolution suggest that diffuse MT1 osteolytic destruction in whole rat vertebrae results primarily in loss of trabeculae in the metastatic vertebrae, as opposed to trabecular thinning. The sensitivity of the bony architectural parameters to resolution motivates the need for high resolution scanning or post-processing of images.

Cortical Perfusion Alteration in Normal-Appearing Gray Matter Is Most Sensitive to Disease Progression in Relapsing-Remitting Multiple Sclerosis

Bookend perfusion was used to quantify parameters in normal-appearing and lesional tissue at different relapsing-remitting MS stages in 39 patients and 19 age-matched healthy controls. Perfusion parameters such as CBF, CBV, and MTT were compared along with cognitive performance. White matter lesion but not cortical lesion perfusion was significantly reduced in cognitively impaired patients with relapsing-remitting MS versus unimpaired patients with relapsing-remitting MS. Perfusion reduction with disease progression was greater in normal-appearing gray matter and normal-appearing white matter compared with cortical lesions and white matter lesions. The authors conclude that the greatest changes are present within NAGM and NAWM, necessitating absolute rather than relative lesion perfusion measurement. BACKGROUND AND PURPOSE: The role of gray matter in multiple sclerosis is increasingly evident; however, conventional images demonstrate limitations in cortical lesion identification. Perfusion imaging appears sensitive to changes in tissue type and disease severity in MS. We sought to use bookend perfusion to quantify parameters in healthy controls and normal-appearing and lesional tissue at different relapsing-remitting MS stages. MATERIALS AND METHODS: Thirty-nine patients with relapsing-remitting MS and 19 age-matched healthy controls were prospectively recruited. The Minimal Assessment of Cognitive Function in MS battery was used to assess cognitive performance. Perfusion parameters, including cerebral blood flow and volume and mean transit time, were compared for healthy controls and normal-appearing and lesional tissue for all study groups. Dispersion of perfusion measures for white matter lesions and cortical lesions was assessed. RESULTS: Twenty of the 39 patients with relapsing-remitting MS were cognitively impaired. Significant differences were displayed between all relapsing-remitting MS subgroups and healthy controls in all comparisons except for normal-appearing gray matter CBV between healthy controls and unimpaired patients with relapsing-remitting MS and for all normal-appearing white matter perfusion parameters between healthy controls and unimpaired patients with relapsing-remitting MS. White matter lesion but not cortical lesion perfusion was significantly reduced in cognitively impaired patients with relapsing-remitting MS versus unimpaired patients with relapsing-remitting MS. Perfusion reduction with disease progression was greater in normal-appearing gray matter and normal-appearing white matter compared with cortical lesions and white matter lesions. Smaller dispersion was observed for cortical lesions compared with white matter lesions for each perfusion parameter. CONCLUSIONS Quantitative GM and WM analysis demonstrated significant but disproportionate white matter lesion, cortical lesion, normal-appearing white matter, and normal-appearing gray matter changes present between healthy controls and patients with relapsing-remitting MS with and without cognitive impairment, necessitating absolute rather than relative lesion perfusion measurement.

A technique for the quantification of the 3D connectivity of thin articulations in Bony sutures

The anatomy and development of cranial and facial sutures have been studied in detail using histological sections, 2D radiographs and more recently CT imaging. However, little attention has been paid to evaluating and quantifying the connectivity of these thin cortical bone articulations. More recent technological advances such as micro-CT imaging has the potential to be used to provide quantitative measurements of 3D connectivity in bony articulations. This study presents a new technique for quantifying the connectivity of bony projections inside cranial and facial sutures using a combination of skeletonization, thinning algorithms and 3D intensity mapping. The technique is demonstrated in five sutures through semi-automated analysis and image processing of microCT scans. In the sagittal, coronal and frontozygomatic sutures an average bone connectivity of 6.6-11.6% was found with multiple bony projections providing an interlocking structure between adjacent bones. Much higher bone connectivity was present in the zygomaticotemporal and zygomaticomaxillary sutures (22.7-37.4%) with few bony projections. This method combining microCT scanning and image processing techniques was successfully used to quantify the connectivity of thin bone articulations and allowed detailed assessment of sutural fusion in 3D. The wider application of this technique may allow quantification of connectivity in other structures, in particular fracture healing of long bones.

Regional Frontal Perfusion Deficits in Relapsing-Remitting Multiple Sclerosis with Cognitive Decline

BACKGROUND AND PURPOSE: Cortical dysfunction, quantifiable by cerebral perfusion techniques, is prevalent in patients with MS, contributing to cognitive impairment. We sought to localize perfusion distribution differences in patients with relapsing-remitting MS with and without cognitive impairment and healthy controls. MATERIALS AND METHODS: Thirty-nine patients with relapsing-remitting MS (20 cognitively impaired, 19 nonimpaired) and 19 age- and sex-matched healthy controls underwent a neurocognitive battery and MR imaging. Voxel-based analysis compared regional deep and cortical GM perfusion and volume among the cohorts. RESULTS: After we adjusted for localized volumetric differences in the right frontal, temporal, and occipital lobes, progressive CBF and CBV deficits were present in the left middle frontal cortex for all cohorts and in the left superior frontal gyrus for patients with cognitive impairment compared with patients without impairment and controls. Compared with healthy controls, reduced CBF was present in the limbic regions of patients with cognitive impairment, and reduced CBV was present in the right middle frontal gyrus in patients with cognitive impairment and in the temporal gyrus of relapsing-remitting MS patients without cognitive impairment. CONCLUSIONS: Consistent regional frontal cortical perfusion deficits are present in patients with relapsing-remitting MS, with more widespread hypoperfusion in those with cognitive impairment, independent of structural differences, indicating that cortical perfusion may be a useful biomarker of cortical dysfunction and cognitive impairment in MS.

Spine labeling in MRI via regularized distribution matching

PurposeThis study investigates an efficient (nearly real-time) two-stage spine labeling algorithm that removes the need for an external training while being applicable to different types of MRI data and acquisition protocols.MethodsBased solely on the image being labeled (i.e., we do not use training data), the first stage aims at detecting potential vertebra candidates following the optimization of a functional containing two terms: (i) a distribution-matching term that encodes contextual information about the vertebrae via a density model learned from a very simple user input, which amounts to a point (mouse click) on a predefined vertebra; and (ii) a regularization constraint, which penalizes isolated candidates in the solution. The second stage removes false positives and identifies all vertebrae and discs by optimizing a geometric constraint, which embeds generic anatomical information on the interconnections between neighboring structures. Based on generic knowledge, our geometric constraint does not require external training.ResultsWe performed quantitative evaluations of the algorithm over a data set of 90 mid-sagittal MRI images of the lumbar spine acquired from 45 different subjects. To assess the flexibility of the algorithm, we used both T1- and T2-weighted images for each subject. A total of 990 structures were automatically detected/labeled and compared to ground-truth annotations by an expert. On the T2-weighted data, we obtained an accuracy of 91.6% for the vertebrae and 89.2% for the discs. On the T1-weighted data, we obtained an accuracy of 90.7% for the vertebrae and 88.1% for the discs.ConclusionOur algorithm removes the need for external training while being applicable to different types of MRI data and acquisition protocols. Based on the current testing data, a subject-specific model density and generic anatomical information, our method can achieve competitive performances when applied to T1- and T2-weighted MRI images.

Comparison of Quantitative Cerebral Blood Flow Measurements Performed by Bookend Dynamic Susceptibility Contrast and Arterial Spin-Labeling MRI in Relapsing-Remitting Multiple Sclerosis

Both dynamic susceptibility contrast perfusion with bookend T1-calibration and pseudocontinuous arterial spin-labeling have been used recently for CBF quantification in relapsing-remitting MS. The authors compared pseudocontinuous arterial spin-labeling CBF with the bookend technique in a prospective cohort of 19 healthy controls, 19 subjects with relapsing-remitting MS without cognitive impairment, and 20 subjects with relapsing-remitting MS with cognitive impairment. Voxelwise paired t tests revealed no significant CBF differences between techniques after normalization of global meanintensities. They conclude that there is agreement between pseudocontinuous arterial spin-labeling and bookend technique CBF measurements in healthy controls and patients with relapsing-remitting MS. BACKGROUND AND PURPOSE: Quantitative CBF usage as a biomarker for cognitive impairment and disease progression in MS is potentially a powerful tool for longitudinal patient monitoring. Dynamic susceptibility contrast perfusion with bookend T1-calibration (bookend technique) and pseudocontinuous arterial spin-labeling have recently been used for CBF quantification in relapsing-remitting MS. The noninvasive nature of pseudocontinuous arterial spin-labeling is advantageous over gadolinium-based techniques, but correlation between the techniques is not well-established in the context of MS. MATERIALS AND METHODS: We compared pseudocontinuous arterial spin-labeling CBF with the bookend technique in a prospective cohort of 19 healthy controls, 19 subjects with relapsing-remitting MS without cognitive impairment, and 20 subjects with relapsing-remitting MS with cognitive impairment on a voxelwise and Brodmann region basis. The linear Pearson correlation, SNR, and coefficient of variation were quantified. RESULTS: Voxelwise paired t tests revealed no significant CBF differences between techniques after normalization of global mean intensities. The highest Pearson correlations were observed in deep GM structures (average r = 0.71 for the basal ganglia and r = 0.65 for the thalamus) but remained robust for cortical GM, WM, and white matter lesions (average r = 0.51, 0.53, 0.54, respectively). Lower Pearson correlations were observed for cortical lesions (average r = 0.23). Brodmann region correlations were significant for all groups. All correlations were maintained in healthy controls and in patients with relapsing-remitting multiple sclerosis. The highest SNR was present in bookend perfusion, while the highest coefficient of variation was present in white matter lesions. CONCLUSIONS: Agreement between pseudocontinuous arterial spin-labeling and bookend technique CBF measurements is demonstrated in healthy controls and patients with relapsing-remitting MS.