Lesion Volume Measurements Research Articles

FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

BackgroundLesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methodsFLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. ResultsFLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. ConclusionThis study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.

Neuroprotective Effect of Human Placenta-Derived Cell Treatment of Stroke in Rats

Human placenta-derived adherent (PDA001) cells are mesenchymal-like stem cells isolated from postpartum placenta. In this study, we tested whether intravenously infused PDA001 improves neurological functional recovery after stroke in rats. In addition, potential mechanisms underlying the PDA001-induced neuroprotective effect were investigated. Young adult male rats (2–3 months) were subjected to 2 h of middle cerebral artery occlusion (MCAo) and treated with PDA001 (4x10(6)) or vehicle controls [dextran vehicle or phosphate buffer saline (PBS)] via intravenous (IV) administration initiated at 4 h after MCAo. A battery of functional tests and measurements of lesion volume and apoptotic cells were performed. Immunostaining and ELISA assays for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) and brain derived neurotrophic factor (BDNF) were performed in the ischemic brain to test the potential mechanisms underlying the neuroprotective effects of PDA001 cell treatment of stroke. PDA001 cell treatment at 4 h post stroke significantly improved functional outcome and significantly decreased lesion volume, TUNEL, and cleaved caspase 3-positive cell number in the ischemic brain, compared to MCAo-vehicle and MCAo-PBS control. Treatment of stroke with PDA001 cells also significantly increased HGF and VEGF expression in the ischemic border zone (IBZ) compared to controls. Using ELISA assays, treatment of stroke with PDA001 cells significantly increased VEGF, HGF, and BDNF levels in the ischemic brain compared to controls. When administered intravenously at 4 h after MCAo, PDA001 cells promoted neuroprotective effects. These effects induced by PDA001 cell treatment may be related to the increase of VEGF, HGF, and BDNF expression,and a decrease of apoptosis. PDA001 cells may provide a viable cell source to treat stroke.

Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy

BackgroundThe exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analysis tools now allow far more subtle assessment of microstructural cerebral changes. The aim of this study was to investigate whether and what severity of subtle structural cerebral changes could lead to CSA-CSR, and whether there is a specific pattern of neurodegenerative changes that cause CSR. Therefore, we examined patients with Fabry disease (FD), an inherited, lysosomal storage disease. White matter lesions are early and frequent findings in FD. Thus, FD can serve as a "model disease" of cerebral microangiopathy to study in more detail the impact of cerebral lesions on central sleep apnea.Patients and MethodsGenetically proven FD patients (n = 23) and age-matched healthy controls (n = 44) underwent a cardio-respiratory polysomnography and brain MRI at 3.0 Tesla. We applied different MR-imaging techniques, ranging from semiquantitative measurement of white matter lesion (WML) volumes and automated calculation of brain tissue volumes to VBM of gray matter and voxel-based diffusion tensor imaging (DTI) analysis.ResultsIn 5 of 23 Fabry patients (22%) CSA-CSR was detected. Voxel-based DTI analysis revealed widespread structural changes in FD patients when compared to the healthy controls. When calculated as a separate group, DTI changes of CSA-CSR patients were most prominent in the brainstem. Voxel-based regression analysis revealed a significant association between CSR severity and microstructural DTI changes within the brainstem.ConclusionSubtle microstructural changes in the brainstem might be a neuroanatomical correlate of CSA-CSR in patients at risk of WML. DTI is more sensitive and specific than conventional structural MRI and other advanced MR analyses tools in demonstrating these abnormalities.

Abstract TP32: ‘ABC/2’ Method for Stroke Measurement has Excellent Intra-Class Correlation for Different Modalities and Raters

BACKGROUND: The ‘Revascularization in Stroke Based on Clinical-Diffusion Mismatch’ study will evaluate the safety of endovascular therapy for stroke patients beyond 8 hours from onset. The inclusion criteria include diffusion weighted magnetic resonance imaging (DW-MRI) stroke lesion volume </=25 mL3. To apply this criterion in practice, measurement techniques easily performed by any clinician, such as the ‘ABC/2’ formula for intracerebral hemorrhage (ICH), are needed. This has been validated against planimetry for middle cerebral artery (MCA) infarction on DW-MRI. We sought to evaluate the inter-rater reliability between raters and the correlation between different ABC/2 formulas for lesions on DWI-MRI and CT. METHODS: CTs and DWI-MRIs of stroke and hemorrhage patients were screened to select a sample of lesions in the cerebral cortex, subcortex, basal ganglia, brainstem, and cerebellum for each group (CT hemorrhage, CT stroke, DW-MRI stroke). Three raters then measured lesion volume as follows: (AxBxC)/2, where A= largest linear lesion diameter in centimeters (cm) on a single slice; B=largest linear diameter perpendicular to A (cm); C=counts between lesion slices multiplied by slice thickness in cm. The ‘adjusted ABC/2’ formula for ICH weights each scan slice by proportion of hemorrhage to the index slice. To evaluate differences between these techniques, a single rater evaluated each lesion using each of the formulas. Measurements were examined through the intraclass correlation (ICC) statistic, to give a composite score of intra-observer and inter-observer variability. The ICC was tested for being significantly different from 0 yielding the reported p-value (1 indicates good ICC). RESULTS: CONCLUSION: The ABC/2 method has excellent ICC on DW-MRI and CT for different examiners, lesions, and locations as well as minimal variability between different formulas. This may be an alternative to computer planimetry for triage of stroke patients in future studies.

Abstract WMP57: Fully Automated CT-based Quantification Of Microangiopathic Density Reduction In White Matter And Comparison To Gold Standard MRI

Purpose: Severity of white matter (WM) lesion load is difficult to quantify precisely in computed tomography (CT) even though it is the most frequently used imaging modality for brain. This pilot study addressed the need for reliable automated observer-independent quantification of white matter disease in CT. The purpose was to present and evaluate a CT-based automated rater independent method for assessment of microangiopathic WM changes. Methods and Materials: A probabilistic WM-tissue-map in standad MNI-152 space was obtained from 600 normal MRI scans from two large population studies (published previously). Robust registration of the WM-tissue-map to individual CT space was accomplished by affine linear registration with non-linear refinement (FSL4.1). The tissue- specific density (Hounsfield Unit, HU) within WM-space of the CT image was determined by the mean of all voxel densities weighted by WM content: Σ (HUxyz × Pxyz (WM))/ Σ (Pxyz (WM) ; (HUxyz = density of voxelxyz ; Pxyz = partial WM content at voxelxyz). The reduction of HU over WM-space in 40 CT images with visible WM disease was correlated with gold standard MR-based WM lesion volume measurements. Results: Automated WM-specific segmentation of brain CT was reliable in 40 cases with varying occurrence of WM-disease. Microangiopathic reduction of density within WM-space showed high correlation with MRI FLAIR-based WM-lesion volume (Pearson correlation coefficient 0.87). Conclusion: Automated quantification of density reduction within WM-space in CT images is feasible and may be used as a surrogate for gold standard MR based WM lesion load. The presented method needs further validation with larger datasets and different CT scanner protocols.

Pingyangmycin with triamcinolone acetonide effective for treatment of lymphatic malformations in the oral and maxillofacial region

ObjectiveThe aim of this study was to evaluate the therapeutic effects of intralesion injection of pingyangmycin in combination with triamcinolone acetonide or pingyangmycin alone on lymphatic malformations in oral and maxillofacial regions. MethodsTwenty-nine cases with lymphatic malformations in the oral and maxillofacial region were divided into experimental and control groups. Thirteen patients in the experimental group underwent intralesion injections of pingyangmycin in combination with triamcinolone acetonide, and 16 patients of control group underwent intralesion injections of pingyangmycin alone. The effects of treatments were assessed by measuring lesion volume and facial deformity before and after treatment. ResultsTwo years after the treatment, the volumes of macrocystic and microcystic lesions were 3.7% ± 0.3 and 4.2% ± 0.4 of pre-treatment volume in the experimental group, respectively, whereas the volumes of macrocystic and microcystic lesions in control group were 15.4% ± 1.3 and 24.1% ± 3.1, respectively. Facial appearance was satisfactory in all subjects in the experimental group, whereas facial asymmetry remained in varying degree in control group. ConclusionIntralesion injection of pingyangmycin with triamcinolone acetonide was more effective than pingyangmycin alone for treatment of lymphatic malformations in oral and maxillofacial regions.

Tract-specific quantitative MRI better correlates with disability than conventional MRI in multiple sclerosis

Although diffusion tensor imaging (DTI) and the magnetization transfer ratio (MTR) have been extensively studied in multiple sclerosis (MS), it is still unclear if they are more effective biomarkers of disability than conventional MRI. MRI scans were performed on 117 participants with MS in addition to 26 healthy volunteers. Mean values were obtained for DTI indices and MTR for supratentorial brain and three white matter tracts of interest. DTI and MTR values were tested for correlations with measures of atrophy and lesion volume and were compared with these more conventional indices for prediction of disability. All DTI and MTR values correlated to an equivalent degree with lesion volume and cerebral volume fraction (CVF). Thalamic volumes correlated with all indices in the optic radiations and with mean and perpendicular diffusivity in the corpus callosum. Nested model regression analysis demonstrated that, compared with CVF, DTI indices in the optic radiations were more strongly correlated with Expanded Disability Status Scale and were also more strongly correlated than both CVF and lesion volume with low-contrast visual acuity. Abnormalities in DTI and MTR are equivalently linked with brain atrophy and inflammatory lesion burden, suggesting that for practical purposes they are markers of multiple aspects of MS pathology. Our findings that some DTI and MTR indices are more strongly linked with disability than conventional MRI measures justifies their potential use as targeted, functional system-specific clinical trial outcomes in MS.

Image-Guided Method in the Rat for Inducing Cortical or Striatal Infarction and for Controlling Cerebral Blood Flow Under MRI

Experimental models are essential for research on ischemic stroke, the second most common cause of death worldwide. The failure of clinical trials on neuroprotective treatment may be due in part to poor animal models. To push the translation of new therapies, we describe a new rat model that captures key elements of human brain ischemia. The model includes imaging and neurointerventional tools that represent the near future of clinical diagnosis and treatment of stroke. Using Sprague-Dawley rats (n=26), we navigated a microwire with fluoroscopy and MRI guidance from the ventral tail artery to 2 different positions in the middle cerebral artery to establish local occlusion. Animals were scanned with 9.4-T MRI before occlusion, during ischemia, and after reperfusion. We detected stroke lesions, corresponding to the level of occlusion, in all animals by diffusion-weighted and T2 images. We measured lesion volume (mm(3)±SD) on T2 scans at 24 hours to be 23.2±29.8 in the somatosensory cortex group and 107.9±80 in the striatum group. We present a new rat model for focal stroke with the possibility to cause lesions in different regions of the brain under fluoroscopic and MRI control. The model will be highly useful for extended studies on the ischemic penumbra, alterations in neural connectivity, and for investigating neurotransmitter-mediated events and biochemical changes in the hyperacute phase of brain ischemia. Also, the model uses clinical routine microcatheters facilitating superselective administration of therapeutics directly to the cerebral circulation.

Workflow-centred evaluation of an automatic lesion tracking software for chemotherapy monitoring by CT

In chemotherapy monitoring, an estimation of the change in tumour size is an important criterion for the assessment of treatment success. This requires a comparison between corresponding lesions in the baseline and follow-up computed tomography (CT) examinations. We evaluate the clinical benefits of an automatic lesion tracking tool that identifies the target lesions in the follow-up CT study and pre-computes the lesion volumes. Four radiologists performed volumetric follow-up examinations for 52 patients with and without lesion tracking. In total, 139 lung nodules, liver metastases and lymph nodes were given as target lesions. We measured reading time, inter-reader variability in lesion identification and volume measurements, and the amount of manual adjustments of the segmentation results. With lesion tracking, target lesion assessment time decreased by 38 % or 22 s per lesion. Relative volume difference between readers was reduced from 0.171 to 0.1. Segmentation quality was comparable with and without lesion tracking. Our automatic lesion tracking tool can make interpretation of follow-up CT examinations quicker and provide results that are less reader-dependent. Computed tomography is widely used to follow-up lesions in oncological patients. Novel software automatically identifies and measures target lesions in oncological follow-up examinations. This enables a reduction of target lesion assessment. The automated measurements are less reader-dependent.

Refinement of the Magnetic Resonance Diffusion-Perfusion Mismatch Concept for Thrombolytic Patient Selection

The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.

Propranolol Reduces Infantile Hemangioma Volume and Vessel Density

To evaluate changes in infantile hemangioma tissue before and after propranolol therapy, using gray-scale and color Doppler ultrasound imaging. Case series with chart review. Tertiary pediatric hospital. Medical records and image studies of head and neck infantile hemangioma patients treated with propranolol, identified in a quality improvement database, were reviewed. Patients with imaging before and at least 4 weeks following the initiation of treatment were included. Data collected included sex, age, location, and concurrent treatment. Student t tests were used to evaluate change in cutaneous lesion area, volume, and vessel density. Logistic regression was used to compare lesion area, volume, and vessel density. Of the 177 patients identified, 19 met inclusion criteria. Fourteen of 19 were female, and 5 of 19 were older than 1 year. Mean lesion area change with treatment was 13.0 cm(2) (range, -2.8 to 28.9 cm(2), P = .05). Measured volume change was a mean of 10.3 cm(3) (range, 1.5-19.2 cm(3), P = .01). Mean vessel density change was 4.4 vessels per cm(2) (range, 2.5-6.3 vessels per cm(2), P < .01). Treatment decreased clinically determined hemangioma area proportionately less than gray-scale and color Doppler ultrasound measured lesion volume. Gray-scale and color Doppler ultrasound measured treatment response did not differ with sex, lesion location, or age at propranolol initiation. Gray-scale and color Doppler ultrasound imaging of propranolol-treated infantile hemangiomas detected a significant reduction in lesion volume and vessel density. Patient age at propranolol treatment and concomitant corticosteroid use did not affect lesion volume change.

Is asymptomatic hemorrhagic transformation really innocuous?

# {#article-title-2} Writ e Click submissions this week reference the article by Dr. Park et al., “Is asymptomatic hemorrhagic transformation really innocuous?” and bring up the possibility of confounding factors in the analysis. Drs. Libman and Kwiatkowski ask that the authors reanalyze their data to adjust for lesion volume. The authors regret that they were not able to measure lesion volume in their study but point out that reports suggest clinical variables are better prognosticators of stroke outcome than radiologic variables. Drs. El-Zammar and Levine suggest the possibility of bias due to stroke etiology, thrombolysis administration, and the statistical handling of disability scores. The authors respond by explaining their statistical methodology but admit the possibility of residual bias despite their adjustments. All agree that analyzing prognostic factors in stroke outcome remains a challenging endeavor. Megan Alcauskas, MD, and Robert C. Griggs, MD Park et al.1 found that patients with asymptomatic hemorrhagic transformation of an infarct had worse functional outcome in 3 months compared to patients without hemorrhagic transformation. The concept of whether asymptomatic hemorrhagic transformation may exert subtle adverse effects that may …

Subject movement during multislice interleaved MR acquisitions: Prevalence and potential effect on MRI-derived brain pathology measurements and multicenter clinical trials of therapeutics for multiple sclerosis

To show the prevalence of inter-packet motion in clinical trial magnetic resonance imaging (MRI) data and the effect of inter-packet motion on MRI-derived brain pathology measurements. We present a method to detect and quantify inter-packet motion, apply it to 2384 MRIs to determine the prevalence of inter-packet motion in clinical trial data, and show the effect of inter-packet motion on measuring multiple sclerosis (MS) lesion volumes. Experiments with simulated data showed that the detection procedure was accurate at measuring the amount of movement between packets and quantifying the amount of missing data. Application to clinical trial data demonstrated that a large number of MRIs had missing data due to inter-packet motion; 20% of the images had greater than 10% of the data missing and 10% of the images had greater than 15% of the data missing. These levels corresponded to thresholds where lesions were difficult to visually identify or disappeared completely. Lesion volume measurement errors ranged from 1.3 ± 0.5% to 9.9 ± 6.3%. Inter-packet motion can introduce substantial errors to MRI-derived brain pathology measurements. The prevalence of inter-packet motion is substantial in MS clinical trial data. Automated detection procedures should be implemented to increase the fidelity of MRI-derived measurements.

Cognitive Reserve Theory May Apply to the Model of Multiple Sclerosis (P03.070)

Objective: To assess the role of overall cognitive reserve along with magnetic resonance (MR) parameters on cognitive functioning over a 1.6+/-0.2 year follow-up in relapsing-remitting (RR) multiple sclerosis (MS). Background Education, premorbid intelligence quotient (IQ) and cognitive leisure have been recently proposed as independent contributors of cognitive reserve in MS patients. Design/Methods: In 35 RRMS patients cognitive functioning was assessed at baseline and at follow-up through the Rao9s Brief Repeatable Battery. A Cognitive Reserve Index (CRI) was calculated including educational level, premorbid leisure activities (Sumowsky et al. 2010) and premorbid IQ estimated through the Brief Intelligence Test. Longitudinal evolution of neuropsychological performance was assessed calculating a reliable change index (RCI). At baseline and follow-up assessments, 31 patients underwent brain MR examination with measurement of T2 and T1 lesion volumes (T2LV and T1LV), total and regional brain volumes and percentage brain volume change (PBVC). Relationships between CRI and cognitive performance were assessed through Spearman correlation, partial correlation and multivariate linear regression analysis. Results: In the total sample at baseline, significant cognitive impairment (CI, failure of >/= 3 tests) was detected in 8 (22.9%) patients. Higher CRI was related with a better performance on tasks of verbal memory, attention, information processing speed and verbal fluency (rho=0.41-0.44,p Conclusions: Consistently with what is reported in research on Alzheimer Disease, also in MS cognitive reserve may mediate between brain pathology and its clinical expression. Therefore, MS patients with higher cognitive reserve are able to withstand more severe brain damage exhibiting a better cognitive performance. Our data support the notion that the “cognitive reserve” theory may apply to the model of MS. Disclosure: Dr. Portaccio has received personal compensation for activities with Biogen Idec as an advisory board member.Dr. Portaccio has received research support from Biogen Idec, Merck Serono, Sanofi Aventis, and Bayer Schering Dr. Razzolini has nothing to disclose. Dr. Goretti has nothing to disclose. Dr. Battaglini has nothing to disclose. Dr. Stromillo has nothing to disclose. Dr. Siracusa has nothing to disclose. Dr. Giorgio has nothing to disclose. Dr. Hakiki has nothing to disclose. Dr. Giannini has nothing to disclose. Dr. Pasto has nothing to disclose. Dr. Sorbi has nothing to disclose. Dr. Federico has nothing to disclose. Dr. De Stefano has received personal compensation for activities with Teva Bayer Schering and Merck Serono International S.A. Dr. De Stefano has received research support from Italian MS Society. Dr. Amato has received personal compensation for activities with Merck Serono, Biogen Dompe, Sanofi-Aventis Pharmaceuticals, and Bayer Schering. Dr. Amato has received research support from Merck Serono, Sanofi-Aventis Pharmaceuticals, Biogen Dompe, and Bayer Schering.

Focal brain trauma in the cryogenic lesion model in mice

The method to induce unilateral cryogenic lesions was first described in 1958 by Klatzo. We describe here an adaptation of this model that allows reliable measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium chloride-staining and Evans blue extravasation in mice. A copper or aluminium cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen and placed on the exposed skull bone over the parietal cortex (coordinates from bregma: 1.5 mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the tip and the parietal skull determine the extent of cryolesion. Due to an early damage of the blood brain barrier, the cryogenic cortical injury is characterized by vasogenic edema, marked brain swelling, and inflammation. The lesion grows during the first 24 hours, a process involving complex interactions between endothelial cells, immune cells, cerebral blood flow, and the intracranial pressure. These contribute substantially to the damage from the initial injury. The major advantage of the cryogenic lesion model is the circumscribed and highly reproducible lesion size and location.

Abstract 3319: Prediction Of Lesion Expansion In Stroke Patients Using Acute MRI

Background: We investigated whether MRI-based algorithms combining acute DWI &amp; PWI can be used to identify patients likely to experience lesion expansion. Methods: We analyzed MRI from 181 unilateral stroke patients who underwent DWI &amp; PWI ≤ 12h from last seen well and had follow-up imaging (F/u) ≥4 days with lesions ≥ 1 cm 3 . Apparent diffusion coefficient, T2, DWI, CBF, CBV, MTT and Tmax (time of peak of deconvolved residue function) maps were co-registered, normalized and used as covariates in a model that produced infarction risk maps. Coefficients were calculated from 111 non-lysed patients and applied to 70 patients who received mechanical or drug lysis. Area under generated receiver operating characteristic curves (AUC) were calculated. Regional analyses were performed comparing mean risk values in Core (acute DWI), Growth (F/u - Core), Reverse (Core - F/u) and Normal (ipsilesional hemisphere - F/u) regions. Predicted lesion volumes (PLV) using a 50% risk threshold and post-hoc artifact removal for classifying infarcted tissue were correlated with the measured lesion volumes (MLV) on F/u. Values are median [IQR] or mean±SD. Results: The thrombolysis-treated group differed significantly from the non-lysis group in admission NIH Stroke Scale scores (12 [9-16] vs 6 [3-13]; P&lt;0.001), time-to-MRI (4.8±1.9 h vs 5.9±2.8 h; P=0.005), acute DWI lesion volumes (21 [7-56] vs 11 [3-36] cm 3 ; P=0.02) and F/u lesion volumes (39 [12-72] vs 17 [6-56] cm 3 ; P=0.02). No significant difference was found between age (67±15 vs 65±17 years old), male sex (59% vs 67%) and time to F/u (15 [6-47] vs 10 [6-46] days). Significant differences in predicted risk between the 4 regions were found for both lysed (Core: 0.72±0.15; Growth: 0.41±0.13; Reverse: 0.64±0.16; Normal: 0.25±0.06; P&lt;0.0001) and non-lysed groups (Core: 0.72±0. 15; Growth:0.42±0.12; Reverse: 0.64±0.15; Normal: 0.22±0.05; P&lt;0.0001). AUCs of the prediction for the non-lysed group were higher than for the lysed group (0.86±0.09 vs 0.81±0.11; P&lt;0.001). Correlations between PLV and MLV were significant for both lysed (R=0.57, P&lt;0.001) and non-lysed groups (R=0.85, P&lt;0.001). Mismatch between PLV and Core volumes (i.e. predicted lesion growth) was significantly correlated with actual lesion growth for the non-lysed group (R=0.49, P&lt;0.001) but not for the lysed group (R=0.04, P=0.72). Conclusion: Mismatch in PLV and core can be used to identify patients most likely to experience lesion expansion if not given reperfusion therapy. The performance of the models was reduced in thrombolysed patients, which we propose is due to salvage of tissue that would have otherwise infarcted. MRI-based algorithms may identify patients who are not candidates for thrombolysis, yet have tissue to salvage. This may be useful as imaging selection criteria for future investigational trials of reperfusion therapy in extended time windows or for patients with unclear onsets.

Abstract 3479: Prediction of Outcome in Cerebellar Infarction by Diffusion MRI

Background and Purpose - Early identification of patients at risk for neurological deterioration after stroke remains a challenge. MRI based volumetric assessments of infarct have been shown to predict poor outcome amongst patients with large middle cerebral artery infarcts. However, no such quantitative imaging measure exists to predict outcome following cerebellar stroke. In this study, we tested the hypothesis that the volume of cerebellar infarction and its associated apparent diffusion coefficient (ADC), as estimated from diffusion-weighted images (DWI), can provide reliable information for the prediction of neurological deterioration. Methods - We retrospectively identified twenty-eight consecutive patients (age 58.2±13) with cerebellar stroke who underwent MRI (median 40.8 hours) with DWI. Patients were divided into poor (N=7) and good (N=21) outcomes. Patients with poor outcome were defined as those who required posterior fossa decompression or died as a result of their cerebellar infarct. Lesion and cerebellar volume were defined on ADC maps. The ratio of the lesion volume to the whole cerebellum volume was calculated (rVolume) as well as the ratio of the lesion mean ADC to normal cerebellum mean ADC (rADC). The National Institutes of Health Stroke Scale (NIHSS) score, as well as age, sex and race were collected. Binary logistic regression was used to identify predictors of poor outcome. The sensitivity and specificity of rVolume and lesion volume were determined in predicting poor outcome using ROC analysis. Results - Logistic regression analysis revealed that rVolume (p=0.018), lesion volume (p=0.034), NIHSS score (p=0.020) and whole cerebellar ADC value (p=0.043) were significant predictors of poor outcome. The rADC (p=0.073) approached significance. The rVolume (p=0.047) remained a significant predictor of outcome even when controlling for age, NIHSS score, and hours to scan, while a trend towards significance for lesion volume (p=0.072), cerebellar ADC (p=0.069) and rADC (p=0.061) were also observed. ROC analysis revealed that both rVolume as a percentage and lesion volume had a specificity of 95% and a sensitivity of 57% in predicting poor outcome. The respective cut-off values were 30% and 41 cc. Conclusions - Quantitative measurement of rVolume, lesion volume, and cerebellar ADC values are significantly correlated with patient outcomes following cerebellar stroke. Although cerebellar ADC provided additional sensitivity, the rVolume appears to be a strong predictor of outcome when controlling for age, NIHSS score and time to scan. Quantitative analysis of diffusion MRI may assist in identification of patients with cerebellar stroke at highest risk of deterioration. Prospective validation is warranted.

Quantitative Evaluation of C-Arm CT Cerebral Blood Volume in a Canine Model of Ischemic Stroke

Previous studies have shown the feasibility of assessing qualitative CBV measurements in the angiography suite by using FPD-CBCT systems. We have investigated the correlation of FPD-CBCT CBV lesion volumes to the infarct volume. Unilateral strokes were created in 7 adult dogs. MR imaging and FPD-CBCT data were obtained after MCA occlusion. FPD-CBCT CBV and ADC maps were generated for all subjects. The animals were sacrificed immediately following the last imaging study to measure infarct volume on histology. The reliability of FPD-CBCT-based lesion volume measurements was compared with those measured histologically by using regression and Bland-Altman analysis. The best correlation (R(2) = 0.72) between lesion volumes assessed with FPD-CBCT and histology was established with a threshold of mean healthy CBV - 2.5 × SD. These results were inferior to the correlation of lesion volumes measured with ADC and histology (R(2) = 0.99). Bland-Altman analysis showed that the agreement of ADC-derived lesion volumes with histology was superior to the agreement of FPD-CBCT-derived lesion volumes with histology. We correlated FPD-CBCT measurements of CBV and MR ADC lesion volumes with histologically assessed infarct volume. As expected, ADC is a very accurate and precise method for determining the extent of infarction. FPD-CBCT CBV lesion volumes are correlated to the size of the infarct. Improvement of FPD-CBCT image quality provides an opportunity to establish quantitative CBV measurement in the angiography suite.

Automated measurement of local white matter lesion volume

It has been hypothesized that white matter lesions at different locations may have different etiology and clinical consequences. Several approaches for the quantification of local white matter lesion load have been proposed in the literature, most of which rely on a distinction between lesions in a periventricular region close to the ventricles and a subcortical zone further away. In this work we present a novel automated method for local white matter lesion volume quantification in magnetic resonance images. The method segments and measures the white matter lesion volume in 43 regions defined by orientation and distance to the ventricles, which allows a more spatially detailed study of lesion load. The potential of the method was demonstrated by analyzing the effect of blood pressure on the regional white matter lesion volume in 490 elderly subjects taken from a longitudinal population study. The method was also compared to two commonly used techniques to assess the periventricular and subcortical lesion load. The main finding was that high blood pressure was primarily associated with lesion load in the vascular watershed area that forms the border between the periventricular and subcortical regions. It explains the associations found for both the periventricular and subcortical load computed for the same data, and that were reported in the literature. But the proposed method can localize the region of association with greater precision than techniques that distinguish between periventricular and subcortical lesions only.

PVE Correction in PET-CT Whole-Body Oncological Studies From PVE-Affected Images

Partial Volume Effect (PVE) in PET-CT oncological studies affects the estimation of quantitative parameters useful for lesion malignancy differentiation and for monitoring disease and response to therapy. The aim of this work was to investigate the clinical feasibility and accuracy of PVE correction methods based on Recovery Coefficients (RC) as function of measured Lesion-to-Background ratio (L/B) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> and measured lesion volume (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> ). PET-CT measurements were performed. The radioactivity concentration (C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> ) and V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> were measured from images using Operator-Dependent and Operator-Independent (OI) techniques. RC curves were obtained combining RC from NEMA 2001 IQ phantom measurements as function of Sphere-to-Background ratio (S/B) <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> and sphere V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> . PVE correction was applied to PET-CT studies of anthropomorphic oncological phantoms and to PET-CT oncological studies (basal and follow up). The underestimation of C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> due to PVE in the NEMA IQ spheres (up to 80%) confirmed the severity of the error. The more feasible (always applicable, noise insensitive, reproducible) way to measure radioactivity was found by the use of an OI threshold technique. Our results showed that this measurement technique allows to achieve a PVE correction accuracy >; 87% (error in radioactivity estimate <; 13%) for a sphere diameter >; 1 cm. In patient studies the PVE correction was found to modify both SUV and SUV variations during patient follow up and our analysis showed that a PVE corrected SUV quantification increases the diagnostic confidence of oncological PET-CT studies.