Personalized treatment planning in eye brachytherapy for ocular melanoma: Dosimetric analysis on ophthalmic structure at risk.

PURPOSE: To evaluate the impact on dose distribution to eye organs-at-risk (eOARs) of a computed tomography (CT)-based treatment planning in eye plaque brachytherapy (EPB) treatment. METHODS: We analyzed 19 ocular melanoma patients treated with ruthenium-106 plaques to a total dose of 100 Gy to tumor apex using conventional central-axis-point dose calculation. Treatments were re-planned using the Plaque Simulator (PS) software implementing two different strategies: a personalized CT-eye-model (CT-PS) and a standard-eye-model (SEM-PS) defined by Collaborative Ocular Melanoma Study. Dice coefficient and Hausdorff distance evaluated the concordance between eye-bulb-models. Mean doses (Dmean) to tumor and eOARs were extracted from Dose-Volume-Histograms and Retinal-Dose-Area-Histogram. Differences between planning approaches were tested by Wilcoxon signed-rank test. RESULTS: In the analyzed cohort, 8 patients (42%) had posterior tumor location, 8 (42%) anterior, and 3 (16%) equatorial. The SEM did not accurately described the real CT eye-bulb geometry (median Hausdorff distance 0.8 mm, range: (0.4-1.3) mm). Significant differences in fovea and macula Dmean values were found (p = 0.04) between CT-PS and SEM-PS schemes. No significant dosimetric differences were found for tumor and other eOARs. The planning scheme particularly affects the OARs closest to the tumor with a general tendency of SEM-PS to overestimate the doses to the OARs closest to the tumor. CONCLUSION: The dosimetric accuracy achievable with CT-PS EPB treatment planning may help to identify ocular melanoma patients who could benefit the most from a personalized eye dosimetry for an optimal outcome in terms of tumor coverage and eOARs sparing. Further research and larger studies are underway.

Serum soluble ST2 is a potential long-term prognostic biomarker for transient ischaemic attack and ischaemic stroke.

BACKGROUND AND PURPOSE: Soluble ST2 (sST2) is a promising biomarker in inflammation, atherosclerosis and cardiovascular diseases. We investigated the association between serum sST2 and poor outcome in patients with transient ischaemic attack (TIA)/ischaemic stroke. METHODS: Patients within 24 h after onset and with measured serum sST2 were prospectively enrolled in this study. Poor outcome was a combination of a new stroke event (ischaemic or haemorrhagic) and all-cause death within 90 days and 1 year. The associations of serum sST2 with poor outcome were analysed by Cox proportional hazards. RESULTS: Among the 430 patients included, the median (interquartile range) sST2 was 17.72 (9.31-28.84) ng/mL. A total of 19 (4.4%) and 38 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Compared with the lowest sST2 tertile, hazard ratios (HRs) [95% confidence intervals (CI)] for the highest tertile were 5.14 (1.43-18.51) for poor outcome within 90 days and 3.00 (1.29-6.97) at 1 year after multivariate adjustments. Adding sST2 to a prediction model significantly improved risk stratification of poor outcome in TIA/ischaemic stroke, as observed by the continuous net reclassification improvement of 60.98% (95% CI, 15.37-106.6%, P = 0.009) and integrated discrimination improvement of 2.63% (95% CI, 0.08-5.18%, P = 0.043) at 90 days and the continuous net reclassification improvement of 41.68% (95% CI, 8.74-74.61%, P = 0.013) at 1 year. CONCLUSIONS: Increased serum sST2 levels in TIA/ischaemic stroke were associated with increased risks of poor outcome within 90 days and 1 year, suggesting that serum sST2 may be a potential long-term prognostic biomarker for TIA/ischaemic stroke.

Rotational radiotherapy of breast cancer with polyenergetic kilovoltage X-ray beams: An experimental and Monte Carlo phantom study.

PURPOSE: We investigated the feasibility of kilovoltage rotational radiotherapy for breast cancer (kV-EBRT) via Monte Carlo simulations and measurements on phantoms. METHODS: We derived the dose distributions for X-ray beams at 150 kV, 300 kVp and 320 kV irradiating breast cylindrical phantoms of 14 cm diameter, mimicking the pendant breast. Simulations were based on the Geant4 toolkit. The point-like X-ray source was rotated either over a full circle or on a limited arc around the phantom. We studied the influence on the surface dose of the distance between the tumor lesion to the skin, of the irradiation protocol (full scan or partial scan) and of the X-ray tube current modulation. RESULTS: Rotational kV-EBRT permitted a periphery-to-center dose ratio from 13% to 9% in homogeneous breast phantoms. Dose distributions in phantoms with off-center simulated lesions, showed a skin-to-tumor dose ratio of 16% and 34% for lesions at 3.25 and 5.25 cm from cylinder axis, respectively. Simulation of the X-ray tube current modulation during the rotation, permits to reach a dose ratio of 20% for the lesion located at 5.25 cm from phantom axis. CONCLUSIONS: We showed the possibility of using low-energy X-ray spectra for kV-EBRT with collimated beams, for obtaining a periphery-to-center dose ratio in the same order of conventional accelerator based megavoltage radiotherapy, when the irradiated area is localized in the center of the breast. For tumors localized near the breast border, we showed that the tube current modulation can be a good solution in order to reduce the skin-to-tumor dose ratio.

Pharmaco-proteomics opportunities for individualizing neurovascular treatment.

Neurovascular disease often involves multi-organ system injury. For example, patent foramen ovale (PFO) related ischemic strokes involve not just the brain, but also the heart, the lung, and the peripheral vascular circulation. For higher-risk but high-reward systemic therapy (e.g., thrombolytics, therapeutic hypothermia (TH), PFO closure) to be implemented safely, very careful patient selection and close monitoring of disease progression and therapeutic efficacy are imperative. For example, more than a decade after the approval of therapeutic hypothermic and intravenous thrombolysis treatments, they both remain extremely under-utilized, in part due to lack of clinical tools for patient selection or to follow therapeutic efficacy. Therefore, in understanding the complexity of the global effects of clinical neurovascular diseases and their therapies, a systemic approach may offer a unique perspective and provide tools with clinical utility. Clinical proteomic approaches may be promising to monitor systemic changes in complex multi-organ diseases - especially where the disease process can be 'sampled' in clinically accessible fluids such as blood, urine, and CSF. Here, we describe a 'pharmaco-proteomic' approach to three major challenges in translational neurovascular research directly at bedside - in order to better stratify risk, widen therapeutic windows, and explore novel targets to be validated at the bench - (i) thrombolytic treatment for ischemic stroke, (ii) therapeutic hypothermia for post-cardiac arrest syndrome, and (iii) treatment for PFO related paradoxical embolic stroke. In the future, this clinical proteomics approach may help to improve patient selection, ensure more precise clinical phenotyping for clinical trials, and individualize patient treatment.

Endovascular approaches to acute stroke, part 2: a comprehensive review of studies and trials.

Reperfusion remains the mainstay of acute ischemic stroke treatment. Endovascular therapy has become a promising alternative for patients who are ineligible for or have failed intravenous (IV) thrombolysis. The conviction that recanalization of properly selected patients is essential for the achievement of good clinical outcomes has led to the rapid and widespread growth in the adoption of endovascular stroke therapies. However, comparisons of the recent reperfusion studies have brought into question the strength of the association between revascularization and improved clinical outcome. Despite higher rates of recanalization, the mechanical thrombectomy studies have demonstrated substantially lower rates of good outcomes compared with IV and/or intra-arterial thrombolytic trials. However, such analyses disregard important differences in clot location and burden, baseline stroke severity, time from stroke onset to treatment, and patient selection in these studies. Many clinical trials are testing novel devices and drugs as well as the paradigm of physiology-based stroke imaging as a treatment-selection tool. The objective of this article is to provide a comprehensive review of the relevant past, current, and upcoming data on endovascular stroke therapy with a special focus on the prospective studies and randomized clinical trials.

Contrast M-mode power Doppler ultrasound in the detection of right-to-left shunts: utility of submandibular internal carotid artery recording.

Cardiac right-to-left shunts (RLSs) can be detected by echocardiography and transcranial Doppler ultrasound (TCD). In patients without adequate transtemporal bone windows, results may be obtained by insonating extracranial arteries; however, the sensitivity and practicality of this approach is unknown. In 34 patients evaluated with echocardiography for RLSs, 73 studies were performed with unilateral, simultaneous contrast TCD (cTCD) of the middle cerebral artery (MCA) and anterior cerebral artery (ACA) and submandibular power M-mode Doppler (PMD) ultrasound of the extracranial internal carotid artery (ecICA). The number of microbubble (MB) signals and their times of first appearance were determined. RLS volume was graded on 6 levels (I = trace, II = small, III = medium, IVa = large, IVb = shower, IVc = curtain) and compared between MCA and ecICA recordings. In 2 of 24 cTCD studies in 15 patients without evidence of RLSs on single-gated MCA monitoring, low-volume RLSs (grades I and II) were detected via ecICA insonation; in both, MB signatures were tracked in the ecICA, passing into the ipsilateral ACA. In 40 of 49 studies (26 patients) in which RLSs were demonstrated with single-gated MCA monitoring, more MBs were detected in the ecICA than the MCA, with either single-gated or M-mode images, with increases of 76.9% and 66.1%, respectively (P = .027). Compared to single-gated studies, M-mode technology detected nonsignificant increases in MB number in both the MCA and the ecICA (by 20.2% and 14.0%, respectively). Contrast PMD with cervical ICA recording is at least as sensitive and specific as the traditional MCA method in detecting RLSs; furthermore, this method seems to be more sensitive for low-volume RLSs (grades I-III) because of air MB decay (9.2%) and entry into the ipsilateral ACA (34.2%). This is in concordance with the increase of detected RLS grades observed in 32.7% of patients with echocardiography-documented RLSs. The authors therefore suggest the incorporation of ecICA PMD not only in patients with poor ultrasonic bone windows but also in every patient being evaluated for suspected RLSs.

Middle cerebral artery territory infarction sparing the precentral gyrus: report of three cases.

We report three patients with large middle cerebral artery infarctions in the non-dominant hemisphere, with striking recovery of motor function. In each case this excellent functional outcome correlated with selective sparing of the motor cortex in the precentral gyrus. We discuss some of the possible circulatory variants that might underlie this pattern of infarction.

Cerebral infarction in conjunction with patent foramen ovale and May-Thurner syndrome.

Stroke patients with paradoxical embolus mandate a search for deep venous thrombosis (DVT) in the lower extremities. Iliac vein compression, or May-Thumer syndrome, places certain patients at risk for development of DVT. The authors present 3 stroke patients with patient foramen ovale and paradoxical cerebral embolism, with demonstrated iliac vein compression as the presumed source of their embolus. May-Thumer syndrome should be considered a potential source of clot, as definitive therapy of this disorder can be curative.

Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis: prediction of final infarct volume and clinical outcome.

BACKGROUND AND PURPOSE: The goal of this study was to evaluate the utility of perfusion-weighted CT (PWCT) in predicting final infarct volume and clinical outcome in patients with acute middle cerebral artery (MCA) stroke. METHODS: Twenty-two consecutive patients with MCA stem occlusion who underwent intra-arterial thrombolysis within 6 hours of stroke onset had noncontrast CT and CT angiography with whole-brain PWCT imaging before treatment. Infarct volumes were computed from the initial PWCT and follow-up scans; clinical outcome was measured with the modified Rankin scale. RESULTS: Initial PWCT lesion volumes correlated significantly with final infarct volume (P=0.0002) and clinical outcome (P=0.01). For the 10 patients with complete recanalization, the relationship between initial and final lesion volume was especially strong (R(2)=0.94, P<0.0001, slope of regression line=0.92). For those without complete recanalization, there was progression of lesion volume on follow-up imaging (R(2)=0.50, P=0.01, slope of regression line=1.61). All patients with either initial PWCT lesion volumes >100 mL or no recanalization had poor outcomes (Rankin scores, 4 to 6). Mean admission NIH Stroke Scale scores and mean lesion volumes in the poor outcome group were significantly different compared with the good or fair outcome (Rankin scores, 0 to 3) group (21+/-4 versus 17+/-5, P=0.05, and 106+/-79 versus 29+/-37 mL, P=0.01). Patients with initial volumes <100 mL and partial or complete recanalization all had good (Rankin scores, 0 to 2) or fair (Rankin score, 3) outcomes. CONCLUSIONS: Lesion volumes on admission PWCT images approximate final infarct volume for patients with early complete recanalization of MCA stem occlusion. For those without complete recanalization, there is subsequent enlargement of lesion volume on follow-up. Initial PWCT lesion volumes also have predictive value; volumes >100 mL are associated with a poor clinical outcome. In these highly selected patients, initial PWCT lesion volume was a stronger predictor of clinical outcome than was initial NIH Stroke Scale score.

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.

A pilot study of drug-induced hypertension for treatment of acute stroke.

The aim of this pilot study was to determine whether the use of induced hypertension in acute stroke is feasible and associated with neurologic improvement. Phenylephrine was used to raise the systolic blood pressure in patients with acute stroke by 20%, not to exceed 200 mmHG: Of 13 patients treated, 7 improved by 2 points on the NIH Stroke SCALE: No systemic or neurologic complications were seen. The authors conclude that induced hypertension in acute stroke is feasible and likely safe and can improve the neurologic examination in some patients.

Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome.

OBJECTIVE: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. BACKGROUND: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. METHODS: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt-Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 degrees C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 degrees C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. RESULTS: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). CONCLUSION: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.

Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. METHODS: Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. RESULTS: At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P=0.02) but no significant improvement over algorithms utilizing PWI alone (P=0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P=0.02) or PWI (P=0.04). The performances of thresholding and GLM algorithms were comparable (P>0.2). CONCLUSIONS: Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.

Localization of clinical syndromes using DWI: two examples of the "capsular" warning syndrome.

The capsular warning syndrome (CWS) is a subtype of transient ischemic attack characterized by its recurrent nature, absence of cortical signs, and high probability of early capsular stroke. Currently, standard imaging techniques have identified only internal capsule lesions in this entity. The authors present 2 cases with an otherwise typical CWS in whom a brainstem stroke was detected by diffusion-weighted imaging (DWI). DWI's ability to differentiate between acute and chronic infarcts may assist in more accurate localization of clinical syndromes.

Diffusion-weighted magnetic resonance imaging identifies the "clinically relevant" small-penetrator infarcts.

BACKGROUND: Most patients initially seen with a clinical syndrome consistent with a small-penetrator infarct (SPI) also harbor multiple, chronic, hyperintense, white matter lesions on conventional magentic resonance imaging (ie, T2-weighted image [T2WI] and fluid-attenuation inversion recovery [FLAIR] imaging). Diffusion-weighted imaging (DWI) can identify the clinically relevant "index infarction" in such circumstances, since it differentiates between acute and chronic lesions. OBJECTIVE: To determine the clinical and radiological predictors associated with misidentification of an SPI as acute using T2WI and FLAIR images in patients with an acute SPI seen on DWI. PATIENTS: Sixty-seven consecutive patients who had an SPI. METHODS: Two independent examiners, provided with brief clinical information, but blinded to DWI findings, sought a clinically appropriate lesion on T2WI and FLAIR imaging in 67 consecutive patients found to have an SPI seen on DWI. RESULTS: The index infarction based on evaluation of T2WI or FLAIR images was in a different location than the acute lesion as identified by DWI in 9 (13%) and 11 (16%) of 67 patients, respectively. Both T2WI and FLAIR imaging were rated normal in another 9% of the patients. Multivariate analysis showed that small lesion size (<10 mm) was the only predictor of misidentifying the clinically appropriate lesion on conventional magnetic resonance imaging (P<.01). CONCLUSIONS: T2-weighted imaging and FLAIR imaging fail to identify the clinically relevant SPI in almost one quarter of the patients found to have a lesion on DWI. The characteristics of DWI make it well suited for the detection of acute small infarcts. Diffusion-weighted imaging is necessary to consistently define the clinical-anatomical relations in patients initially seen with SPIs.

Diffusion-weighted imaging identifies a subset of lacunar infarction associated with embolic source.

BACKGROUND AND PURPOSE: Small infarcts in the territory of penetrator arteries were described as causing a number of distinct clinical syndromes. The vascular pathophysiology underlying such infarcts is difficult to ascertain without careful pathological study. However, the occurrence of multiple, small infarcts, linked closely in time but dispersed widely in the brain, raises the possibility of an embolic mechanism. The current study determines the frequency and clinical characteristics of patients with well-defined lacunar syndromes and the diffusion-weighted imaging (DWI) evidence of multiple acute lesions. METHODS: Sixty-two consecutive patients who presented to the emergency room with a clinically well-defined lacunar syndrome were studied by DWI within the first 3 days of admission. RESULTS: DWI showed multiple regions of increased signal intensity in 10 patients (16%). A hemispheric or brain stem lesion in a penetrator territory that accounted for the clinical syndrome ("index lesion") was found in all. DWI-hyperintense lesions other than the index lesion ("subsidiary infarctions") were punctate and lay within leptomeningeal artery territories in the majority. As opposed to patients with a single lacunar infarction, patients with a subsidiary infarction more frequently (P<0.05) harbored an identifiable cause of stroke. CONCLUSIONS: Almost 1 of every 6 patients presenting with a classic lacunar syndrome has multiple infarctions demonstrated on DWI. This DWI finding usually indicates an identifiable cause of stroke and therefore may influence clinical decisions regarding the extent of etiologic investigations and treatment for secondary prevention.

Cerebral venous sinus thrombosis associated with hepatic cirrhosis.

Cerebral venous sinus thrombosis is not a recognized complication of end-stage liver disease. A case of sagittal sinus thrombosis in a 44-year-old male with end-stage hepatic cirrhosis is described. Recurrent seizures were the only manifestation. Work-up revealed severe deficiency of protein C, protein S, and antithrombin III. He was treated with low molecular weight heparin and underwent an orthotopic liver transplant after three months. Follow-up helical CT venogram showed resolution of the sinus thrombosis.

Lack of evidence of an association between mitral-valve prolapse and stroke in young patients.

BACKGROUND: Previous studies have reported a high prevalence of mitral-valve prolapse among patients with embolic stroke (28 to 40 percent), especially among young patients (those < or =45 years old); this finding has practical implications for prophylaxis. However, diagnostic criteria for prolapse have changed and are now based on three-dimensional analysis of the shape of the valve; use of the current criteria reduces markedly the frequency of such a diagnosis and increases its specificity. Previously described complications must therefore be reconsidered. METHODS: In a case-control study, we reviewed data on 213 consecutive patients 45 years old or younger with documented ischemic stroke or transient ischemic attack between 1985 and 1995; they underwent complete neurologic and echocardiographic evaluations. The prevalence of prolapse in these patients was compared with that in 263 control subjects without known heart disease, who were referred to our institution for assessment of ventricular function before receiving chemotherapy. RESULTS: Mitral-valve prolapse was present in 4 of the 213 young patients with stroke (1.9 percent), as compared with 7 of the 263 controls (2.7 percent); prolapse was present in 2 of 71 patients (2.8 percent) with otherwise unexplained stroke. The crude odds ratio for mitral-valve prolapse among the patients who had strokes, as compared with those who did not have strokes, was 0.70 (95 percent confidence interval, 0.15 to 2.80; P=0.80); after adjustment for age and sex, the odds ratio was 0.59 (95 percent confidence interval, 0.12 to 2.50; P=0.62). CONCLUSIONS: Mitral-valve prolapse is considerably less common than previously reported among young patients with stroke or transient ischemic attack, including unexplained stroke, and no more common than among controls. Using more specific and currently accepted echocardiographic criteria, therefore, we could not demonstrate an association between the presence of mitral-valve prolapse and acute ischemic neurologic events in young people.

Normal diffusion-weighted MRI during stroke-like deficits.

BACKGROUND: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. OBJECTIVE: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. METHODS: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. RESULTS: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). CONCLUSIONS: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.

Hyperacute stroke: simultaneous measurement of relative cerebral blood volume, relative cerebral blood flow, and mean tissue transit time.

PURPOSE: To investigate additional information provided by maps of relative cerebral blood flow in functional magnetic resonance (MR) imaging of human hyperacute cerebral ischemic stroke. MATERIALS AND METHODS: Diffusion-weighted and hemodynamic MR imaging were performed in 23 patients less than 12 hours after the onset of symptoms. Maps of relative cerebral blood flow and tracer mean tissue transit time were computed, as were maps of apparent diffusion and relative cerebral blood volume. Acute lesion volumes on the maps were compared with follow-up imaging findings. RESULTS: In 15 of 23 subjects (65%), blood flow maps revealed hemodynamic abnormalities not visible on blood volume maps. A mismatch between initial blood flow and diffusion findings predicted growth of infarct more often (12 of 15 subjects with infarcts that grew) than did a mismatch between initial blood volume and diffusion findings (eight of 15). However, lesion volumes on blood volume and diffusion maps correlated better with eventual infarct volumes (r > 0.90) than did those on blood flow and tracer mean transit time maps (r approximately 0.6), likely as a result of threshold effects. In eight patients, blood volume was elevated around the diffusion abnormality, suggesting a compensatory hemodynamic response. CONCLUSION: MR imaging can delineate areas of altered blood flow, blood volume, and water mobility in hyperacute human stroke. Predictive models of tissue outcome may benefit by including computation of both relative cerebral blood flow and blood volume.