Raphael Jakubovic

CT perfusion spot sign improves sensitivity for prediction of outcome compared with CTA and postcontrast CT

BACKGROUND AND PURPOSE: Recent studies have recommended both early and late imaging to increase spot sign detection. However optimal acquisition timing for spot detection and impact on outcome prediction is uncertain. Our aim was to assess the utility of CTP in spot sign detection and characterization with emphasis on its impact on the prediction of outcome in patients with acute primary ICH. MATERIALS AND METHODS: A retrospective review of 28 patients presenting within 6 hours of ICH, studied with CTA, CTP, and postcontrast CT, was performed. CTA, CTP, and postcontrast CT spot sign characteristics were recorded according to predefined radiologic criteria. A combined primary outcome of hematoma expansion or poor clinical outcome was used and defined as hematoma expansion ≥6 mL or ≥30%, need for surgical drainage, or in-hospital mortality. Associations with the primary outcome and spot sign presence were examined against baseline clinical, laboratory, and radiographic variables. Predictive ability of CTA, CTP, and postcontrast CT spot characteristics were compared among modalities. RESULTS: Primary outcome criteria were met in 18 patients (61%). CTP spot sign presence was an independent predictor of hematoma expansion or poor outcome (P = .040) and demonstrated greater sensitivity (78%) than spots detected on CTA (44%, P = .034) and postcontrast CT (50%, P = .025). Specificity and positive predictive value of the spot sign was high (100%) on all modalities. CTP detected the greatest number of spots (80%) with peak spot attenuation demonstrated at a median (interquartile range) time of 50 seconds (range, 34–63 seconds) after contrast bolus injection. CTP spot appearance was later than CTA-detected spots (P = .002) and earlier than postcontrast CT spots (P < .001). CONCLUSIONS: CTP spot sign detection improves the sensitivity for prediction of outcome compared with CTA or postcontrast CT–detected spots.

Robust Perfusion Deficits in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis

These authors investigated the effect of perfusion deficits on patients with MS with cognitive impairment. In 45 patients with secondary-progressive MS, cognition was assessed using standardized clinical tests and CBF and CBV perfusion maps were obtained, analyzed, and correlated with gray and white matter and lesion volumes. Perfusion in the deep gray matter nuclei and frontal cortex was significantly reduced in cognitively impaired patients with MS despite no significant differences regarding gray matter, white matter, and lesion volumes. Of the cognitive parameters investigated, information processing speed was most affected. BACKGROUND AND PURPOSE: Cognitive impairment is a common, disabling symptom of MS. We investigated the impact of cerebral perfusion and brain and lesion volumetry on cognitive performance in 45 patients with SPMS by using MR imaging. MATERIALS AND METHODS: Cognition was assessed by using a standard battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. qCBF and qCBV maps were analyzed by using SPM and PLS. SPM was also used to conduct the GM, WM, and WML volumetric analyses. RESULTS: Both SPM and PLS demonstrated significantly reduced qCBV in the superior medial frontal cortex of impaired patients. PLS also revealed significantly lower qCBV in the bilateral thalami and caudate nuclei of impaired patients and identified a pattern of significantly attenuated qCBF similar to that of qCBV. Performance on the Symbol Digit Modalities Test, which assesses information-processing speed, correlated most strongly overall with cerebral perfusion. Focal (ie, voxelwise) analyses of GM, WM, and WML volume revealed no significant differences between patients with and without cognitive impairment, though global GM volume was significantly decreased and global WML volume was significantly increased in impaired patients. CONCLUSIONS: These results suggest that cognitively impaired patients with SPMS exhibit robust perfusion deficits in cortical and subcortical GM and impaired processing speed.

Toward Patient-Tailored Perfusion Thresholds for Prediction of Stroke Outcome

BACKGROUND AND PURPOSE: Multiple patient-specific clinical and radiologic parameters impact traditional perfusion thresholds used to classify/determine tissue outcome. We sought to determine whether modified baseline perfusion thresholds calculated by integrating baseline perfusion and clinical factors better predict tissue fate and clinical outcome. MATERIALS AND METHODS: CTP within 4.5 hours of acute anterior circulation stroke onset and 5- to 7-day MR imaging were performed for 203 patients with stroke, divided into derivation (n = 114) and validation (n = 89) data bases. Affected regions were operationally classified as infarct and noninfarct according to baseline CTP and follow-up FLAIR imaging. Perfusion thresholds were derived for each of the infarct and noninfarct regions, without and with transformation by baseline clinical and radiologic variables by using a general linear mixed model. Performance of transformed and nontransformed perfusion thresholds for tissue fate and 90-day clinical outcome prediction was then tested in the derivation data base. Reproducibility of models was verified by using bootstrapping and validated in an independent cohort. RESULTS: Perfusion threshold transformation by clinical and radiologic baseline parameters significantly improved tissue fate prediction for both gray matter and white matter (P < .001). Transformed thresholds improved the 90-day outcome prediction for CBF and time-to-maximum (P < .001). Transformed relative CBF and absolute time-to-maximum values demonstrated maximal GM and WM accuracies in the derivation and validation cohorts (relative CBF GM: 91%, 86%; WM: 86%, 83%; absolute time-to-maximum 88%, 79%, and 80%, 76% respectively). CONCLUSIONS: Transformation of baseline perfusion parameters by patient-specific clinical and radiologic parameters significantly improves the accuracy of tissue fate and clinical outcome prediction.

Intracerebral hemorrhage: toward physiological imaging of hemorrhage risk in acute and chronic bleeding

Despite improvements in management and prevention of intracerebral hemorrhage (ICH), there has been little improvement in mortality over the last 30 years. Hematoma expansion, primarily during the first few hours is highly predictive of neurological deterioration, poor functional outcome, and mortality. For each 10% increase in ICH size, there is a 5% increase in mortality and an additional 16% chance of poorer functional outcome. As such, both the identification and prevention of hematoma expansion are attractive therapeutic targets in ICH. Previous studies suggest that contrast extravasation seen on CT Angiography (CTA), MRI, and digital subtraction angiography correlates with hematoma growth, indicating ongoing bleeding. Contrast extravasation on the arterial phase of a CTA has been coined the CTA Spot Sign. These easily identifiable foci of contrast enhancement have been identified as independent predictors of hematoma growth, mortality, and clinical outcome in primary ICH. The Spot Sign score, developed to stratify risk of hematoma expansion, has shown high inter-observer agreement. Post-contrast leakage or delayed CTA Spot Sign, on post contrast CT following CTA or delayed CTA respectively are seen in an additional ∼8% of patients and explain apparently false negative observations on early CTA imaging in patients subsequently undergoing hematoma expansion. CT perfusion provides an opportunity to acquire dynamic imaging and has been shown to quantify rates of contrast extravasation. Intravenous recombinant factor VIIa (rFVIIa) within 4 h of ICH onset has been shown to significantly reduce hematoma growth. However, clinical efficacy has yet to be proven. There is compelling evidence that cerebral amyloid angiopathy (CAA) may precede the radiographic evidence of vascular disease and as such contribute to microbleeding. The interplay between microbleeding, CAA, CTA Spot Sign and genetic composition (ApoE genotype) may be crucial in developing a risk model for ICH.

Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases.

PURPOSE To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). METHODS Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. RESULTS Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. CONCLUSION Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio.

Spinal intraoperative three-dimensional navigation: correlation between clinical and absolute engineering accuracy

BACKGROUND CONTEXT Spinal intraoperative computer-assisted navigation (CAN) may guide pedicle screw placement. Computer-assisted navigation techniques have been reported to reduce pedicle screw breach rates across all spinal levels. However, definitions of screw breach vary widely across studies, if reported at all. The absolute quantitative error of spinal navigation systems is theoretically a more precise and generalizable metric of navigation accuracy. It has also been computed variably and reported in less than a quarter of clinical studies of CAN-guided pedicle screw accuracy. PURPOSE This study aimed to characterize the correlation between clinical pedicle screw accuracy, based on postoperative imaging, and absolute quantitative navigation accuracy. DESIGN/SETTING This is a retrospective review of a prospectively collected cohort. PATIENT SAMPLE We recruited 30 patients undergoing first-time posterior cervical-thoracic-lumbar-sacral instrumented fusion±decompression, guided by intraoperative three-dimensional CAN. OUTCOME MEASURES Clinical or radiographic screw accuracy (Heary and 2 mm classifications) and absolute quantitative navigation accuracy (translational and angular error in axial and sagittal planes). METHODS We reviewed a prospectively collected series of 209 pedicle screws placed with CAN guidance. Each screw was graded clinically by multiple independent raters using the Heary and 2 mm classifications. Clinical grades were dichotomized per convention. The absolute accuracy of each screw was quantified by the translational and angular error in each of the axial and sagittal planes. RESULTS Acceptable screw accuracy was achieved for significantly fewer screws based on 2 mm grade versus Heary grade (92.6% vs. 95.1%, p=.036), particularly in the lumbar spine. Inter-rater agreement was good for the Heary classification and moderate for the 2 mm grade, significantly greater among radiologists than surgeon raters. Mean absolute translational-angular accuracies were 1.75 mm-3.13° and 1.20 mm-3.64° in the axial and sagittal planes, respectively. There was no correlation between clinical and absolute navigation accuracy. CONCLUSIONS Radiographic classifications of pedicle screw accuracy vary in sensitivity across spinal levels, as well as in inter-rater reliability. Correlation between clinical screw grade and absolute navigation accuracy is poor, as surgeons appear to compensate for navigation registration error. Future studies of navigation accuracy should report absolute translational and angular errors. Clinical screw grades based on postoperative imaging may be more reliable if performed in multiple by radiologist raters.

Extensive White Matter Dysfunction in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis

BACKGROUND AND PURPOSE: Cognitive impairment is a common, disabling symptom of MS. We investigated the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis using DTI. MATERIALS AND METHODS: Cognitive performance was assessed with a standard neuropsychological battery, the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests. Fractional anisotropy maps were compared against cognitive status using tract-based spatial statistics with threshold-free cluster enhancement. RESULTS: Forty-five patients with secondary-progressive multiple sclerosis (median age: 55 years, female/male: 27/18, median Expanded Disability Status Scale Score: 6.5) were prospectively recruited. Cognitively impaired patients (25/45) displayed significantly less normalized global GM and WM volumes (P = .001, P = .024), more normalized T2-weighted and T1-weighted WM lesion volumes (P = .002, P = .006), and lower WM skeleton fractional anisotropy (P < .001) than non-impaired patients. Impaired patients also had significantly lower fractional anisotropy (pcorr < .05) in over 50% of voxels within every major WM tract. The most extensively impinged tracts were the left posterior thalamic radiation (100.0%), corpus callosum (97.8%), and right sagittal stratum (97.5%). No WM voxels had significantly higher fractional anisotropy in patients with cognitive impairment compared with their non-impaired counterparts (pcorr > .05). After the inclusion of confounders in a multivariate logistic regression, only fractional anisotropy remained a significant predictor of cognitive status. CONCLUSIONS: Cognitively impaired patients with secondary-progressive multiple sclerosis exhibited extensive WM dysfunction, though preferential involvement of WM tracts associated with cognition, such as the corpus callosum, was apparent. Multivariate analysis revealed that only WM skeleton fractional anisotropy was a significant predictor of cognitive status.

Normal-Appearing White Matter Permeability Distinguishes Poor Cognitive Performance in Processing Speed and Working Memory

BACKGROUND AND PURPOSE: Secondary-progressive MS is characterized by reduced acute inflammation and contrast enhancement but with increased axonal degeneration and cognitive/clinical disability that worsens with advanced disease. Relative recirculation, extracted from DSC is a surrogate measure of BBB integrity. We hypothesized that normal-appearing white matter relative recirculation is reduced in cognitively impaired compared with nonimpaired secondary-progressive MS, reflecting more advanced disease. MATERIALS AND METHODS: Cognitive performance was classified as impaired or nonimpaired by use of Minimal Assessment of Cognitive Function In MS test components. Demographic data, brain parenchymal fraction, WM lesion fraction, and weighted mean normal-appearing white matter relative recirculation were compared in cognitively dichotomized groups. Univariate and multivariate logistic regressions were used to study the association between cognitive test results and normal-appearing white matter relative recirculation. RESULTS: The mean (SD) age of 36 patients with secondary-progressive MS studied was 55.9 ± 9.3 years; 13 of 36 (36%) patients were male. A highly significant difference between normal-appearing white matter relative recirculation and WM lesion relative recirculation was present for all patients (P < .001). Normal-appearing white matter relative recirculation in impaired patients was significantly lower than in nonimpaired subjects for the Symbol Digit Modalities Test (P = .007), Controlled Word Association Test (P = .008), and Paced Auditory Serial Addition Test (P = .024). The Expanded Disability Status Scale demonstrated an inverse correlation with normal-appearing white matter relative recirculation (r = −0.319, P = .075). After adjustment for confounders, significant normal-appearing white matter relative recirculation reduction persisted for the Symbol Digit Modalities Test (P = .023) and the Paced Auditory Serial Addition Test (P = .047) but not for the Controlled Word Association Test (P = .13) in impaired patients. CONCLUSIONS: Significant normal-appearing white matter relative recirculation reduction exists in cognitively impaired patients with secondary-progressive MS, localizing to the domains of processing speed and working memory.

High speed, wide velocity dynamic range Doppler optical coherence tomography (Part V): Optimal utilization of multi-beam scanning for Doppler and speckle variance microvascular imaging

In this paper, a multi-beam scanning technique is proposed to optimize the microvascular images of human skin obtained with Doppler effect based methods and speckle variance processing. Flow phantom experiments were performed to investigate the suitability for combining multi-beam data to achieve enhanced microvascular imaging. To our surprise, the highly variable spot sizes (ranging from 13 to 77 μm) encountered in high numerical aperture multi-beam OCT system imaging the same target provided reasonably uniform Doppler variance and speckle variance responses as functions of flow velocity, which formed the basis for combining them to obtain better microvascular imaging without scanning penalty. In vivo 2D and 3D imaging of human skin was then performed to further demonstrate the benefit of combining multi-beam scanning to obtain improved signal-to-noise ratio (SNR) in microvascular imaging. Such SNR improvement can be as high as 10 dB. To our knowledge, this is the first demonstration of combining different spot size, staggered multiple optical foci scanning, to achieve enhanced SNR for blood flow OCT imaging.

High-Frequency Micro-Ultrasound Imaging and Optical Topographic Imaging for Spinal Surgery: Initial Experiences

High frequency micro-ultrasound (µUS) transducers with central frequencies up to 50 MHz facilitate dynamic visualization of patient anatomy with minimal disruption of the surgical work flow. Micro-ultrasound improves spatial resolution over conventional ultrasound imaging from millimeter to micrometer, but compromises depth penetration. This trade-off is sufficient during an open surgery in which the bone is removed and theultrasound probe can be placed into the surgical cavity. By fusing µUS with pre-operative imaging and tracking the ultrasound probe intra-operatively using our optical topographic imaging technology, we can provide dynamic feedback during surgery, thus affecting clinical decision making. We present our initial experience using high-frequency µUS imaging during spinal procedures. Micro-ultrasound images were obtained in five spinal procedures. Medical rationale for use of µUS was provided for each patient. Surgical procedures were performed using the standard clinical practice with bone removal to facilitate real-time ultrasound imaging of the soft tissue. During surgery, the µUS probe was registered to the pre-operative computed tomography and magnetic resonance images. Images obtained comprised five spinal decompression surgeries (four tumor resections, one cystic synovial mass). Micro-ultrasound images obtained during spine surgery delineated exquisite detailing of the spinal anatomy including white matter and gray matter tracts and nerve roots and allowed accurate assessment of the extent of decompression/tumor resection. In conclusion, tracked µUS enables real-time imaging of the surgical cavity, conferring significant qualitative improvement over conventional ultrasound.