Clinical utility of arterial spin labeling perfusion images in the emergency department for the work-up of stroke-like symptoms.

PURPOSE: To assess the utility of ASL in evaluating patients presenting to the ED with stroke-like symptoms. METHODS: ASL and DWI images from 526 consecutive patients presenting to the ED with acute stroke symptoms were retrospectively reviewed. DWI images were evaluated for volume of restricted diffusion using ABC/2. ASL maps were evaluated for decreased, normal, or increased signal. The volume of decreased ASL signal was calculated using the same ABC/2 technique. The volume of decreased ASL signal was correlated with the volume of DWI signal abnormality to identify cases of mismatch (DWI:ASL ratio > 1.8) and to correlate this mismatch with infarct growth on imaging follow-up. NIHSS, length of hospital stay, mRS, and future admission for acute stroke-like symptoms were recorded. Correlations between ASL abnormalities and clinical parameters were evaluated using a two-tailed t-test. RESULTS: Of the 526 patients presenting with acute stroke symptoms, 136 patients had an abnormal ASL scan and 388 patients had a normal ASL scan. Of the 136 patients with abnormal ASL, 84 patients had low ASL signal with 79 of these being related to acute infarcts. Elevated ASL signal was seen in 52 patients, of which 30 of these patients had reperfusion hyperemia related to acute infarctions. ASL had a negative predictive value of 94% for evaluating patients with acute ischemic stroke. A subset of patients with abnormal ASL scans with a discharge diagnosis of acute infarction were found to have an ASL:DWI mismatch (ratio > 1.8) and demonstrated significant lesion growth on follow-up imaging (57%). This included some patients who exhibited low ASL signal before development of diffusion restriction (infarction). CONCLUSION: In patients presenting to the ED with acute stroke symptoms, ASL provides information not available with DWI alone. The NPV of ASL for evaluating patients with acute ischemia was 94%.

Imaging of Atlanto-Occipital and Atlantoaxial Traumatic Injuries: What the Radiologist Needs to Know.

Approximately one-third of all cervical spine injuries involve the craniocervical junction (CCJ). Composed of the occiput and the first two cervical vertebrae, this important anatomic landmark, in conjunction with an intricate ligamentous complex, is essential to maintaining the stability of the cervical spine. The atlantoaxial joint is the most mobile portion of the spine, predominantly relying on the ligamentous framework for stability at that level. As acute onsite management of trauma patients continues to improve, CCJ injuries, which often lead to death onsite where the injury occurred, are increasingly being encountered in the emergency department. Understanding the anatomy of the CCJ is crucial in properly evaluating the cervical spine, allowing the radiologist to assess its stability in the trauma setting. The imaging findings of important CCJ injuries, such as atlanto-occipital dissociation, occipital condyle fractures, atlas fractures with transverse ligament rupture, atlantoaxial distraction, and traumatic rotatory subluxation, are important to recognize in the acute setting, often dictating patient management. Thin-section multidetector computed tomography with sagittal and coronal reformats is the study of choice in evaluating the extent of injury, allowing the radiologist to thoroughly evaluate the stability of the cervical spine. Furthermore, magnetic resonance (MR) imaging is increasingly being used to evaluate the spinal soft tissues and ligaments, and to identify associated spinal cord injury, if present. MR imaging is also indicated in patients whose neurologic status cannot be evaluated within 48 hours of injury. .

Time and diffusion lesion size in major anterior circulation ischemic strokes.

BACKGROUND AND PURPOSE: Major anterior circulation ischemic strokes caused by occlusion of the distal internal carotid artery or proximal middle cerebral artery or both account for about one third of ischemic strokes with mostly poor outcomes. These strokes are treatable by intravenous tissue-type plasminogen activator and endovascular methods. However, dynamics of infarct growth in these strokes are poorly documented. The purpose was to help understand infarct growth dynamics by measuring acute infarct size with diffusion-weighted imaging (DWI) at known times after stroke onset in patients with documented internal carotid artery/middle cerebral artery occlusions. METHODS: Retrospectively, we included 47 consecutive patients with documented internal carotid artery/middle cerebral artery occlusions who underwent DWI within 30 hours of stroke onset. Prospectively, 139 patients were identified using the same inclusion criteria. DWI lesion volumes were measured and correlated to time since stroke onset. Perfusion data were reviewed in those who underwent perfusion imaging. RESULTS: Acute infarct volumes ranged from 0.41 to 318.3 mL. Infarct size and time did not correlate (R2=0.001). The majority of patients had DWI lesions that were <25% the territory at risk (<70 mL) whether they were imaged <8 or >8 hours after stroke onset. DWI lesions corresponded to areas of greatly reduced perfusion. CONCLUSIONS: Poor correlation between infarct volume and time after stroke onset suggests that there are factors more powerful than time in determining infarct size within the first 30 hours. The observations suggest that highly variable cerebral perfusion via the collateral circulation may primarily determine infarct growth dynamics. If verified, clinical implications include the possibility of treating many patients outside traditional time windows.

Acute ischemic stroke: infarct core estimation on CT angiography source images depends on CT angiography protocol.

PURPOSE: To test whether the relationship between acute ischemic infarct size on concurrent computed tomographic (CT) angiography source images and diffusion-weighted (DW) magnetic resonance images is dependent on the parameters of CT angiography acquisition protocols. MATERIALS AND METHODS: This retrospective study had institutional review board approval, and all records were HIPAA compliant. Data in 100 patients with anterior-circulation acute ischemic stroke and large vessel occlusion who underwent concurrent CT angiography and DW imaging within 9 hours of symptom onset were analyzed. Measured areas of hyperintensity at acute DW imaging were used as the standard of reference for infarct size. Information regarding lesion volumes and CT angiography protocol parameters was collected for each patient. For analysis, patients were divided into two groups on the basis of CT angiography protocol differences (patients in group 1 were imaged with the older, slower protocol). Intermethod agreement for infarct size was evaluated by using the Wilcoxon signed rank test, as well as by using Spearman correlation and Bland-Altman analysis. Multivariate analysis was performed to identify predictors of marked (≥20%) overestimation of infarct size on CT angiography source images. RESULTS: In group 1 (n=35), median hypoattenuation volumes on CT angiography source images were slightly underestimated compared with DW imaging hyperintensity volumes (33.0 vs 41.6 mL, P=.01; ratio=0.83), with high correlation (ρ=0.91). In group 2 (n=65), median volume on CT angiography source images was much larger than that on DW images (94.8 vs 17.8 mL, P<.0001; ratio=3.5), with poor correlation (ρ=0.49). This overestimation on CT angiography source images would have inappropriately excluded from reperfusion therapy 44.4% or 90.3% of patients eligible according to DW imaging criteria on the basis of a 100-mL absolute threshold or a 20% or greater mismatch threshold, respectively. Atrial fibrillation and shorter time from contrast material injection to image acquisition were independent predictors of marked (≥20%) infarct size overestimation on CT angiography source images. CONCLUSION: CT angiography protocol changes designed to speed imaging and optimize arterial opacification are associated with significant overestimation of infarct size on CT angiography source images.

Rapid identification of a major diffusion/perfusion mismatch in distal internal carotid artery or middle cerebral artery ischemic stroke.

BACKGROUND: We tested the hypothesis that in patients with occlusion of the terminal internal carotid artery and/or the proximal middle cerebral artery, a diffusion abnormality of 70 ml or less is accompanied by a diffusion/perfusion mismatch of at least 100%. METHODS: Sixty-eight consecutive patients with terminal ICA and/or proximal MCA occlusions and who underwent diffusion/perfusion MRI within 24 hours of stroke onset were retrospectively identified. DWI and mean transit time (MTT) volumes were measured. Prospectively, 48 consecutive patients were identified with the same inclusion criteria. DWI and time to peak (TTP) lesion volumes were measured. A large mismatch volume was defined as an MTT or TTP abnormality at least twice the DWI lesion volume. RESULTS: In the retrospective study, 49 of 68 patients had a DWI lesion volume ≤ 70 ml (mean 20.2 ml; SEM 2.9 ml). A DWI/MTT mismatch of > 100% was observed in all 49 patients (P < .0001). In the prospective study, there were 35/48 patients with DWI volumes ≤ 70 ml (mean 18.7 ml; SEM 3.0 ml). A mismatch > 100% was present in all 35 (P < .0001). CONCLUSIONS: Acute stroke patients with major anterior circulation artery occlusion are exceedingly likely to have a major diffusion/perfusion mismatch if the diffusion lesion volume is 70 ml or less. This suggests that physiology-based patient assessments may be made using only vessel imaging and diffusion MRI as a simple alternative to perfusion imaging.

A radiologist's guide to novel anticancer therapies in the era of precision medicine.

Novel anticancer agents have replaced conventional chemotherapy as first line agents for many cancers, with continued new and expanding indications. Small molecule inhibitors act on cell surface or intracellular targets and prevent the downstream signaling that would otherwise permit tumor growth and spread. Anticancer antibodies can be directed against growth factors or may be immunotherapeutic agents. The latter act by inhibiting mechanisms that cancer cells use to evade the immune system. Hormonal agents act by decreasing levels of hormones that are necessary for the growth of certain cancer cells. Cancer therapy protocols often include novel anticancer agents and conventional chemotherapy used successively or in combination, in order to maximize survival and minimize morbidity. A working knowledge of anti-cancer drug classification will aid the radiologist in assessing response on imaging.

Brain creatine elevation and N-Acetylaspartate reduction indicates neuronal dysfunction in the setting of enhanced glial energy metabolism in a macaque model of neuroAIDS.

Proton magnetic resonance spectroscopy has emerged as one of the most informative neuroimaging modalities for studying the effect of HIV infection in the brain, providing surrogate markers by which to assess disease progression and monitor treatment. Reductions in the level of N-Acetylaspartate and N-Acetylaspartate/creatine are established markers of neuronal injury or loss. However, the biochemical basis of altered creatine levels in neuroAIDS is not well understood. This study used a rapid progression macaque model of neuroAIDS to elucidate the changes in creatine. As the disease progressed, proton magnetic resonance spectroscopy revealed a decrease in N-Acetylaspartate, indicative of neuronal injury, and an increase in creatine yet to be elucidated. Subsequently, immunohistochemistry and stereology measures of decreased synaptophysin, microtubule-associated protein 2, and neuronal density confirmed neuronal injury. Furthermore, increases in ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein indicated microglial and astroglial activation, respectively. Given these data, elevated creatine may reflect enhanced high-energy phosphate turnover in highly metabolizing activated astrocytes and microglia.

The safety and effectiveness of a curved needle for vertebral augmentation: comparison with traditional techniques.

PURPOSE: To evaluate the safety and effectiveness of a curved needle compared with traditional (noncurved needle) techniques in a large single-center experience. MATERIALS AND METHODS: This study was a retrospective analysis of 243 consecutive vertebral augmentation procedures over a 17-month period. Curved needle procedures were compared with noncurved needle procedures for baseline clinical variables, complication rate, pain relief, and improvement in disability. Procedure duration and fluoroscopy time were compared between the two cohorts. RESULTS: Between curved needle and noncurved needle procedures, there were no statistically significant differences in the baseline clinical variables, fracture location, and fracture etiology. No complications were noted in either group. In both groups, there was a median improvement in the visual analog scale (VAS) score of 2.0 points (P = .62). More than 90% of procedures in both groups resulted in some pain improvement (P = .78). For both groups, the median improvement in disability on the Roland Morris Disability Questionnaire (RMDQ) was 4.0 points (P = .69). Approximately 70% of procedures in both groups resulted in improvement in disability (P = 1.00). In single-level cases, there were shorter procedure times (51.8 min ± 2.7 vs 62.8 min ± 2.2, P = .002) and shorter fluoroscopy times (P = .31) for curved needle procedures. CONCLUSIONS: The curved needle is as safe and effective as traditional vertebral augmentation techniques in treating the pain and disability related to vertebral compression fractures. Additionally, the curved needle is associated with shorter procedure duration and reduced fluoroscopy time.

Stability of large diffusion/perfusion mismatch in anterior circulation strokes for 4 or more hours.

BACKGROUND: The stability of hypoperfused brain tissue in stroke patients with major artery occlusions is unknown. The purpose of this study was to determine the persistence of a diffusion/perfusion mismatch in patients with ICA or proximal MCA occlusions. METHODS: Fourteen patients with ICA and/or proximal MCA occlusion and a diffusion/perfusion mismatch at presentation were studied. All were enrolled in a pilot randomized study of normobaric oxygen therapy. None received thrombolytic therapy; 8 received normobaric oxygen and 6 room air. Diffusion/perfusion MRI was performed at baseline, 4 hours, 24 hours, and 1 week. Abnormal DWI, ADC, and MTT volumes were determined using standard image analysis methods. RESULTS: The mean time from symptom onset to baseline MRI was 7.5 +/- 1 hours. Across all 4 time points there was a significant difference in DWI lesion (ANOVA, P < 0.0001) and abnormal MTT volumes (ANOVA, P < 0.01) with the 24 hour and 1 week abnormal volumes different from the earlier studies. However, comparing baseline and 4 hour scans, there was no significant interval change in the mean abnormal DWI volume (29.4 +/- 8.2 ml vs. 28.1 +/- 7.4 ml) or abnormal MTT volumes (137 +/- 17.7 ml vs. 130.9 +/- 13.8). By 24 hours, only 2 patients did not maintain a mismatch of 20% or greater. CONCLUSIONS: Patients who present outside the time window for thrombolytic therapy, and who have a large diffusion/perfusion mismatch on MRI may have a stable mismatch for 4 or more hours.

Predictors of functional outcome vary by the hemisphere of involvement in major ischemic stroke treated with intra-arterial therapy: a retrospective cohort study.

BACKGROUND: Conflicting data exists regarding the effect of hemispheric lateralization on acute ischemic stroke outcome. Some of this variability may be related to heterogeneous study populations, particularly with respect to the level of arterial occlusion. Furthermore, little is known about the relationship between stroke lateralization and predictors of outcome. The purpose of this study was to characterize the impact of stroke lateralization on both functional outcome and its predictors in a well-defined population of anterior circulation proximal artery occlusions treated with IAT. METHODS: Thirty-five consecutive left- and 35 consecutive right-sided stroke patients with intracranial ICA and/or MCA occlusions who underwent IAT were retrospectively analyzed. Ischemic change on pre-treatment imaging was quantified. Reperfusion success was graded using the Mori scale. Good outcome at three months was defined as an mRS

Longitudinal Analysis of Quantitative Brain MRI in Astronauts Following Microgravity Exposure.

BACKGROUND AND PURPOSE: Assessment of the effects of microgravity on astronauts' brains using microstructural measures by utilizing quantitative MRI, before and after spaceflight would help understand the structural changes. METHODS: Quantitative MRI data sets in 19 astronauts were acquired before and after space missions. Both diffusion tensor metrics and volumetric measures were analyzed in the brain regions involved in the visual function. RESULTS: The fractional anisotropy was reduced in the right posterior thalamic radiations (P = .0009) and remained significant after a false discovery rate (FDR) correction (P = .03). A trend of increase in the mean diffusivities of different subregions of the occipital cortex on the right side, including calcarine, middle occipital, inferior occipital, and fusiform gyri, was noted and became insignificant after FDR correction. Similarly, there was a trend of cortical thinning involving the right occipital lobe and bilateral fusiform gyri, volume reduction of the left thalamus, and increase in lateral ventricular volume in the postflight scans. CONCLUSION: Gray and white matter alterations are detected by quantitative MRI before and after space flight. Our findings may be used to understand the neuroanatomical mechanisms of possible brain dysfunction or neuroplasticity in microgravity condition in the future studies.

A direct aspiration first-pass technique vs stentriever thrombectomy in emergent large vessel intracranial occlusions.

OBJECTIVE Endovascular thrombectomy in patients with acute ischemic stroke caused by occlusion of the proximal anterior circulation arteries is superior to standard medical therapy. Stentriever thrombectomy with or without aspiration assistance was the predominant technique used in the 5 randomized controlled trials that demonstrated the superiority of endovascular thrombectomy. Other studies have highlighted the efficacy of a direct aspiration first-pass technique (ADAPT). METHODS To compare the angiographic and clinical outcomes of ADAPT versus stentriever thrombectomy in patients with emergent large vessel occlusions (ELVO) of the anterior intracranial circulation, the records of 134 patients who were treated between June 2012 and October 2015 were reviewed. RESULTS Within this cohort, 117 patients were eligible for evaluation. ADAPT was used in 47 patients, 20 (42.5%) of whom required rescue stentriever thrombectomy, and primary stentriever thrombectomy was performed in 70 patients. Patients in the ADAPT group were slightly younger than those in the stentriever group (63.5 vs 69.4 years; p = 0.04); however, there were no differences in the other baseline clinical or radiographic factors. Procedural time (54.0 vs 77.1 minutes; p < 0.01) and time to a Thrombolysis in Cerebral Infarction (TICI) scale score of 2b/3 recanalization (294.3 vs 346.7 minutes; p < 0.01) were significantly lower in patients undergoing ADAPT versus stentriever thrombectomy. The rates of TICI 2b/3 recanalization were similar between the ADAPT and stentriever groups (82.9% vs 71.4%; p = 0.19). There were no differences in the rates of symptomatic intracranial hemorrhage or procedural complications. The rates of good functional outcome (modified Rankin Scale Score 0-2) at 90 days were similar between the ADAPT and stentriever groups (48.9% vs 41.4%; p = 0.45), even when accounting for the subset of patients in the ADAPT group who required rescue stentriever thrombectomy. CONCLUSIONS The present study demonstrates that ADAPT and primary stentriever thrombectomy for acute ischemic stroke due to ELVO are equivalent with respect to the rates of TICI 2b/3 recanalization and 90-day mRS scores. Given the reduced procedural time and time to TICI 2b/3 recanalization with similar functional outcomes, an initial attempt at recanalization with ADAPT may be warranted prior to stentriever thrombectomy.

Novel finding of optic nerve central T2 hypointensity utilizing 3 Tesla MR imaging.

We sought to report a central T2 hypointensity within the optic nerve on 3 T MRI studies obtained as part of the NASA Flight Medicine Visual Impairment Intracranial Pressure Protocol that had not been described previously. Twenty-one astronauts, who had undergone MRI of both orbits with direct coronal T2 sequences between 2010 and 2012, were retrospectively included. Two of the astronauts did not have previous exposure to microgravity at the time of their scans. A central T2 hypointensity was observed in 100% of both right and left eyes. It was completely visualized throughout the nerve course in 15 right eyes (71.4%) and in 19 left eyes (90.5%).We describe a new finding seen in all study participants: a central T2 hypointensity in the epicenter of the optic nerve. We speculate that this T2 hypointensity may represent flow voids caused by the central retinal vessels.

Safety of full-dose intravenous recombinant tissue plasminogen activator followed by multimodal endovascular therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: The optimal management of stroke patients who fail treatment with intravenous recombinant tissue plasminogen activator (rt-PA) remains unknown. A study was undertaken to establish whether treatment with a standard intravenous t-PA dose (0.9 mg/kg) followed by multimodal endovascular therapy would have a similar safety profile to reduced dose (0.6 mg/kg) bridging therapy. METHODS: A retrospective analysis was performed of a prospectively collected database. All patients treated with full-dose t-PA and endovascular therapy were included. The primary safety endpoints included ECASS-III symptomatic intracranial hemorrhage (sICH) and ECASS parenchymal hematomas (PH). Secondary safety endpoints included severe systemic bleeding and 90-day mortality. Clinical efficacy endpoints included rates of recanalization (TICI 2-3), ambulation at hospital discharge and 90-day independent outcomes (mRS 0-2). RESULTS: 106 consecutive patients (mean age 69 ± 17 years; mean baseline NIH Stroke Scale 17.8 ± 4.8; 55% women; occlusion sites: MCA-M1 60.4%; MCA-M2 6.6%; ICA-T 19.8%; tandem cervical ICA+MCA-M1 7.5%; basilar artery 5.7%) were identified over a 10-year period. The sICH rate was 8.5% and the PH-1, PH-2 and subarachnoid hemorrhage rates were 2.8%, 8.5% and 2.8%, respectively. There were two (1.9%) severe groin hematomas. The recanalization rate was 66%. At hospital discharge, 41.4% of the patients were ambulatory. The rate of independent functional outcomes at 90 days was 24%; however, this sample is biased since nearly all deaths were captured but detailed 90-day functional outcomes were missing in 27 patients. The 90-day death rate was 32.4%. CONCLUSION: Combined treatment with full-dose intravenous rt-PA followed by multimodal endovascular therapy seems to be associated with similar rates of sICH to that of bridging therapy with reduced rt-PA dosage.

CT angiography source images acquired with a fast-acquisition protocol overestimate infarct core on diffusion weighted images in acute ischemic stroke.

BACKGROUND AND PURPOSE: Studies have demonstrated that computed tomography (CT) angiography source images (CTA-SI) acquired under near-steady-state contrast concentration provide infarct core estimates equivalent to diffusion-weighted images (DWI). We sought to test this relationship using our current CTA protocol optimized for faster scan acquisition. METHODS: Forty-eight consecutive acute ischemic stroke patients met the following criteria: fast-acquisition CTA and magnetic resonance imaging (MRI) within 9 hours of symptom onset, CTA-to-MRI interval under 2 hours, and anterior circulation vessel occlusion. Collaterals were graded on CTA, and lesion volumes were calculated on CTA-SI, DWI, and MR mean transit time (MTT) maps. RESULTS: The mean CTA-to-MRI interval was 36 minutes (± 18 minutes). In paired analysis, lesion volumes on CTA-SI were significantly larger than on DWI (45.6 cm3 vs. 29.9 cm3; P < .0001). In 14 (29.2%) cases, there was major CTA-SI overestimation (>25 cm3 difference) of the DWI lesion. Lower collateral score (P = .001), higher National Institutes of Health stroke scale (NIHSS) score (P = .01), older age (P = .01), and proximal occlusion (P < .05) were univariate predictors of major overestimation, with collateral score being the only independent predictor. The interobserver agreement was worse for CTA-SI than for DWI (P < .001 for limits of agreement). CONCLUSIONS: CTA-SI performed using a fast-acquisition protocol overestimates the infarct core on DWI. Substantial differences are observed in over 25% of cases, and are associated with reduced collateralization.

CT angiography predicts use of tertiary interventional services in acute ischemic stroke patients.

BACKGROUND: Patients with acute stroke are often transferred to tertiary care centers for advanced interventional services. We hypothesized that the presence of a proximal cerebral artery occlusion on CT angiography (CTA) is an independent predictor of the use of these services. METHODS: We performed a historical cohort study of consecutive ischemic stroke patients presenting within 24 h of symptom onset to an academic emergency department who underwent emergent CTA. Use of tertiary care interventions including intra-arterial (IA) thrombolysis, mechanical clot retrieval, and neurosurgery were captured. RESULTS: During the study period, 207/290 (71%) of patients with acute ischemic stroke underwent emergent CTA. Of the patients, 74/207 (36%) showed evidence of a proximal cerebral artery occlusion, and 22/207 (11%) underwent an interventional procedure. Those with proximal occlusions were more likely to receive a neurointervention (26% vs. 2%, p < 0.001). They were more likely to undergo IA thrombolysis (9% vs. 0%, p = 0.001) or a mechanical intervention (19% vs. 0%, p < 0.0001), but not more likely to undergo neurosurgery (5% vs. 2%, p = 0.2). After controlling for the initial NIH stroke scale (NIHSS) score, proximal occlusion remained an independent predictor of the use of neurointerventional services (OR 8.5, 95% CI 2.2-33). Evidence of proximal occlusion on CTA predicted use of neurointervention with sensitivity of 82% (95% CI 59-94%), specificity of 71% (95% CI 64%-77%), positive predictive value (PPV) of 25% (95% CI 16%-37%), and negative predictive value (NPV) of 97% (95% CI 92%-99%). CONCLUSION: Proximal cerebral artery occlusion on CTA predicts the need for advanced neurointerventional services.

Diffusion weighted imaging reversibility in the brainstem following successful recanalization of acute basilar artery occlusion.

Acute basilar artery occlusion (ABAO) is a devastating disease that can produce significant brainstem injury. Pretreatment diffusion weighted imaging (DWI) demonstrating extensive brainstem involvement has been shown to predict a poor outcome regardless of reperfusion. This case report describes a patient presenting with coma secondary to ABAO. MRI at presentation demonstrated significant DWI abnormality in the majority of the bilateral pons. The basilar artery was endovascularly recanalized 8 h after stroke onset, and the patient had a marked clinical recovery with no deficit at 3 months. Follow-up imaging revealed significant reversal of the pontine lesion. This finding of brainstem DWI reversibility cautions against the use of DWI to select ABAO patients for intra-arterial stroke therapy. The degree of apparent diffusion coefficient reduction on pretreatment MRI may not adequately identify which DWI abnormal brainstem tissue is potentially reversible.

Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated NeuroAIDS.

BACKGROUND: Despite the advent of highly active anti-retroviral therapy (HAART), HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV) macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. METHODOLOGY/PRINCIPAL FINDINGS: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi). Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN), microtubule-associated protein 2 (MAP2), and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr), which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals. CONCLUSIONS/SIGNIFICANCE: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus.

Neuroimaging of ischemic stroke with CT and MRI: advancing towards physiology-based diagnosis and therapy.

Acute ischemic stroke is the third leading cause of death and the major cause of significant disability in adults in the USA and Europe. The number of patients who are actually treated for acute ischemic stroke is disappointingly low, despite availability of effective treatments. A major obstacle is the short window of time following stroke in which therapies are effective. Modern imaging is able to identify the ischemic penumbra, a key concept in stroke physiology. Evidence is accumulating that identification of a penumbra enhances patient management, resulting in significantly improved outcomes. Moreover, unexpectedly large proportions of patients have a substantial ischemic penumbra beyond the traditional time window and are suitable for therapy. The widespread availability of modern MRI and computed tomography systems presents new opportunities to use physiology to guide ischemic stroke therapy in individual patients. This article suggests an evidence-based alternative to contemporary acute ischemic stroke therapy.