R. Gilberto Gonzalez

Reward circuitry activation by noxious thermal stimuli.

Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degrees C) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum. In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli.

Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study

Brain activity was studied with functional magnetic resonance imaging (fMRI) following thermal stimulation. Two groups (n = 6/group) of human male volunteers were given up to four noxious (46°C) and four non‐noxious (41°C) stimuli. In the 46°C experiment, positive signal changes were found in the frontal gyri, anterior and posterior cingulate gyrus, thalamus, motor cortex, somatosensory cortex (SI and SII), supplementary motor area, insula, and cerebellum. Low‐level negative signal changes appeared in the amygdala and hypothalamus. All regions activated by 46°C were also activated by 41°C. However, except for SI and thalamus, significantly more activation was observed for the 46°C stimulus. A significant attenuation of the signal change was observed by the third stimulus for the 46°C, but not for 41°C experiment. Similar findings were replicated in the second group. These fMRI findings specify differences between somatosensory and pain sensation and suggest a number of rich avenues for future research. Magn Reson Med 41:1044–1057, 1999.

Diffusion-Weighted Imaging Discriminates Between Cytotoxic and Vasogenic Edema in a Patient With Eclampsia

BACKGROUND The pathophysiology of eclampsia remains unclear. While the majority of patients develop reversible T2 hyperintense signal abnormalities on MR scans and reversible neurological deficits, some patients do develop infarctions (permanent T2 hyperintense abnormalities) and permanent neurological impairment. Routine MRI cannot prospectively differentiate between these two patient groups. Echo-planar diffusion-weighted imaging, however, is a new technique that clearly differentiates between cytotoxic and vasogenic edema. CASE DESCRIPTION A 30-year-old woman developed symptoms consistent with eclampsia 24 hours after delivering premature twins. An MRI demonstrated extensive, diffuse T2 hyperintense signal abnormalities involving subcortical white matter and adjacent gray matter with a posterior predominance, consistent with either infarction or hypertensive ischemic encephalopathy. Diffusion-weighted images demonstrated increased diffusion, consistent with vasogenic edema and hypertensive ischemic encephalopathy. CONCLUSIONS Unlike routine MRI, diffusion-weighted imaging reliably differentiates between vasogenic edema and cytotoxic edema. Consequently, in eclamptic patients diffusion-weighted imaging can afford clear differentiation between hypertensive ischemic encephalopathy and infarction, two very different entities with very different treatment protocols. Diffusion-weighted imaging should be performed in all eclamptic patients and should greatly affect their management.

CT angiography in the rapid triage of patients with hyperacute stroke to intraarterial thrombolysis: accuracy in the detection of large vessel thrombus.

Purpose The purpose of this work was to evaluate the accuracy of CT angiography (CTA) for the detection of large vessel intracranial thrombus in clinically suspected hyperacute (<6 h) stroke patients. Method Forty-four consecutive intraarterial thrombolysis candidates underwent noncontrast CT followed immediately by CTA. Axial source and two-dimensional collapsed maximum intensity projection reformatted CTA images were rated for the presence or absence of large vessel occlusion. Five hundred seventy-two circle-of-Willis vessels were reviewed; arteriographic correlation was available for 224 of these. Results Sensitivity and specificity for the detection of large vessel occlusion were 98.4 and 98.1%; accuracy, calculated using receiver operating characteristic analysis, was 99%. Mean time for acquisition, reconstruction, and analysis of CTA images was approximately 15 min. Conclusion CTA is highly accurate for the detection and exclusion of large vessel intracranial occlusion and may therefore be valuable in the rapid triage of hyperacute stroke patients to intraarterial thrombolytic treatment.

MRI-Based Selection for Intra-Arterial Stroke Therapy Value of Pretreatment Diffusion-Weighted Imaging Lesion Volume in Selecting Patients With Acute Stroke Who Will Benefit From Early Recanalization

Background and Purpose— Recent studies demonstrate that an acute diffusion-weighted imaging lesion volume >70 cm3 predicts poor outcome in patients with stroke. We sought to determine if this threshold could identify patients treated with intra-arterial therapy who would do poorly despite reperfusion. In patients with initial infarcts <70 cm3, we sought to determine what effect recanalization and time to recanalization had on infarct growth and functional outcome. Methods— We retrospectively studied 34 consecutive patients with anterior circulation stroke who underwent pretreatment diffusion-weighted imaging and perfusion-weighted imaging and subsequent intra-arterial therapy. Recanalization success and time to recanalization were recorded. Initial diffusion-weighted imaging and mean transit time lesion and final infarct volumes were determined. Patients were stratified based on initial infarct volume, recanalization status, and time to recanalization. Statistical tests were performed to assess differences in clinical and imaging outcomes. Good clinical outcome was defined as a 3-month modified Rankin Scale score ≤2. Results— Among patients with initial infarcts >70 cm3, all had poor outcomes despite a 50% recanalization rate with mean infarct growth of 114 cm3. These patients also had the largest mean transit time volumes (P<0.04). Patients with initial infarct volumes <70 cm3 who recanalized early had the best clinical outcomes (P<0.008) with a 64% rate of modified Rankin Scale score ≤2 and the least infarct growth (P<0.03) with mean growth of 18 cm3. Conclusion— This study supports the use of an acute diffusion-weighted imaging lesion volume threshold as an imaging selection criterion for intra-arterial therapy. It also confirms the importance of early reperfusion in selected patients.

A Pilot Study of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Background and Purpose— Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. Methods— We randomized patients with acute stroke (<12 hours) and perfusion-diffusion “mismatch” on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. Results— Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (±SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8±22% versus 149.1±41%; P=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline “ischemic” to 4-hour “non-ischemic” values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These “during-therapy” benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (P=0.6). Conclusions— High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.

Diffusion-weighted imaging for the evaluation of diffuse axonal injury in closed head injury

Purpose The purpose of this work was to compare diffusion-weighted imaging (DWI) with conventional MRI in the detection of shearing injuries in acute closed head injuries. Method Twenty-five patients (19 male, 6 female) were examined within 48 h of trauma. Conventional MRI included T2-weighted fast spin echo, fluid-attenuated inversion recovery (FLAIR), and T2*-weighted gradient echo sequences. Full tensor DWI with calculation of apparent diffusion coefficient (ADC) maps was also performed. Lesions were identified and compared on all sequences. Results Four hundred twenty-seven lesions were counted by the combined use of all sequences. DWI identified 70 lesions not seen on conventional MRI. DWI identified 310 shearing injuries, followed by T2/FLAIR (n = 248) and T2* (n = 202). The majority of DWI-positive lesions showed decreased diffusion (65%). Conclusion DWI is valuable in closed head injury because it identifies additional shearing injuries not visible on T2/FLAIR or T2* sequences. Furthermore, DWI/ADC maps differentiate between lesions with decreased or increased diffusion. DWI is less sensitive than T2* imaging for detecting hemorrhagic lesions.

Acute plasticity in the human somatosensory cortex following amputation.

WE studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals.

Somatotopic Activation in the Human Trigeminal Pain Pathway

Functional magnetic resonance imaging was used to image pain-associated activity in three levels of the neuraxis: the medullary dorsal horn, thalamus, and primary somatosensory cortex. In nine subjects, noxious thermal stimuli (46°C) were applied to the facial skin at sites within the three divisions of the trigeminal nerve (V1, V2, and V3) and also to the ipsilateral thumb. Anatomical and functional data were acquired to capture activation across the spinothalamocortical pathway in each individual. Significant activation was observed in the ipsilateral spinal trigeminal nucleus within the medulla and lower pons in response to at least one of the three facial stimuli in all applicable data sets. Activation from the three facial stimulation sites exhibited a somatotopic organization along the longitudinal (rostrocaudal) axis of the brain stem that was consistent with the classically described “onion skin” pattern of sensory deficits observed in patients after trigeminal tractotomy. In the thalamus, activation was observed in the contralateral side involving the ventroposteromedial and dorsomedial nuclei after stimulation of the face and in the ventroposterolateral and dorsomedial nuclei after stimulation of the thumb. Activation in the primary somatosensory cortex displayed a laminar sequence that resembled the trigeminal nucleus, with V2 more rostral, V1 caudal, and V3 medial, abutting the region of cortical activation observed for the thumb. These results represent the first simultaneous imaging of pain-associated activation at three levels of the neuraxis in individual subjects. This approach will be useful for exploring central correlates of plasticity in models of experimental and clinical pain.

Systematic characterization of the computed tomography angiography spot sign in primary intracerebral hemorrhage identifies patients at highest risk for hematoma expansion: the spot sign score.

Background and Purpose— The presence of active contrast extravasation (the spot sign) on computed tomography (CT) angiography has been recognized as a predictor of hematoma expansion in patients with intracerebral hemorrhage. We aim to systematically characterize the spot sign to identify features that are most predictive of hematoma expansion and construct a spot sign scoring system. Methods— We retrospectively reviewed CT angiograms performed in all patients who presented to our emergency department over a 9-year period with primary intracerebral hemorrhage and had a follow-up noncontrast head CT within 48 hours of the baseline CT angiogram. Three neuroradiologists reviewed the CT angiograms and determined the presence and characteristics of spot signs according to strict radiological criteria. Baseline and follow-up intracerebral hemorrhage volumes were determined by computer-assisted volumetric analysis. Results— We identified spot signs in 71 of 367 CT angiograms (19%), 6 of which were delayed spot signs (8%). The presence of any spot sign increased the risk of significant hematoma expansion (69%, OR=92, P<0.0001). Among the spot sign characteristics examined, the presence of ≥3 spot signs, a maximum axial dimension ≥5 mm, and maximum attenuation ≥180 Hounsfield units were independent predictors of significant hematoma expansion, and these were subsequently used to construct the spot sign score. In multivariate analysis, the spot sign score was the strongest predictor of significant hematoma expansion, independent of time from ictus to CT angiogram evaluation. Conclusion— The spot sign score predicts significant hematoma expansion in primary intracerebral hemorrhage. If validated in other data sets, it could be used to select patients for early hemostatic therapy.