Longitudinal MRI findings in patients with newly diagnosed glioblastoma after intraoperative radiotherapy.

BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV. RESULTS: Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], P = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (P = 0.001) and T2 lesion volumes (P < 0.001) in the longitudinal non-parametric analysis in comparison to the control group. rCBV showed no significant differences between both groups. CONCLUSIONS: High doses of radiotherapy to the tumor cavity result in more pronounced enhancement patterns/volumes and T2 lesion volumes. These results will be useful for the response evaluation of patients exposed to high doses of radiotherapy in future studies.

Gadolinium Leakage in Ocular Structures Is Common in Lacunar Infarction.

Background and Purpose- We investigated the frequency and pattern of blood-brain barrier, as well as blood-retina barrier, impairment in acute lacunar infarction as demonstrated by hyperintense acute reperfusion marker and gadolinium leakage in ocular structures (GLOS), respectively, on fluid-attenuated inversion recovery images. Methods- Acute lacunar infarction patients who underwent repeated magnetic resonance imaging after intravenous contrast agent administration were identified and the presence of GLOS in the anterior chamber and vitreous body and hyperintense acute reperfusion marker noted on fluid-attenuated inversion recovery. Results- Overall, 24 acute lacunar infarction patients (median age 64.5 years; interquartile range, 54-78 years) were included. On contrast-enhanced fluid-attenuated inversion recovery, GLOS was observed in 11 (45.8%) patients: in 4 (16.7%) in the anterior chamber only and in 7 (29.2%) in the anterior chamber and vitreous body. In all patients, GLOS was bilateral and symmetrical. In patients with GLOS in the anterior chamber only, the time between initial and follow-up magnetic resonance imaging was significantly shorter (7.5 [interquartile range, 4.25-11.5] hours) compared with patients with GLOS in the anterior chamber and vitreous body (28 [interquartile range, 10-43] hours; P=0.047). Hyperintense acute reperfusion marker could not be demonstrated in any of the patients. Conclusions- In acute lacunar infarction patients, unlike hyperintense acute reperfusion marker, GLOS is a frequent finding and shows a similar temporal evolution like in larger ischemic stroke.

Contrast-enhanced fat-suppressed FLAIR for the characterization of leptomeningeal inflammation in optic neuritis.

BACKGROUND: Leptomeningeal contrast enhancement on fluid-attenuated inversion recovery (FLAIR) images has been reported in patients with multiple sclerosis and interpreted as a biomarker of inflammation. In this study, we sought to evaluate this phenomenon in patients with optic neuritis (ON). METHODS: A total of 42 patients with suspected ON were included in this prospective study and underwent a dedicated study magnetic resonance imaging (MRI) protocol including native and contrast-enhanced fat-suppressed thin-section axial and coronal FLAIR images on an 1.5 T magnetic resonance (MR) system. RESULTS: After diagnostic workup, 34 patients with final diagnosis of ON were analyzed in detail. On contrast-enhanced fat-suppressed FLAIR images, 25 (73.5%) patients with ON demonstrated perioptic leptomeningeal enhancement, and in 3 (8.8%) patients, this was even the only pathological MRI finding. In comparison, patients with perioptic leptomeningeal enhancement on contrast-enhanced fat-suppressed FLAIR images had a higher prevalence of additional hyperintense brain lesions ( p = 0.022) as well as cerebrospinal fluid (CSF)-specific oligoclonal bands ( p = 0.013) than patients without. CONCLUSION: Perioptic leptomeningeal contrast enhancement on fat-suppressed FLAIR images is a novel marker in ON and possibly reflects a leptomeningeal inflammatory process preceding or accompanying ON. Thin-section contrast-enhanced fat-suppressed FLAIR images might be a useful addition in MRI protocols for patients with suspected ON.

Heterogeneity of glioblastoma with gliomatosis cerebri growth pattern on diffusion and perfusion MRI.

BACKGROUND AND PURPOSE: Gliomatosis cerebri (GC) is a rare growth pattern of glioblastoma whose diffuse nature is reflected by unspecific, relatively uniform findings on conventional MRI. In the present study we sought to evaluate the additional value of diffusion (DWI) and perfusion weighted (PWI) MRI for a more detailed characterization. METHODS: We analyzed the MRI findings in patients with histologically proven glioblastoma with GC growth pattern with a specific emphasis on T2 lesion pattern, volume, relative apparent diffusion coefficient (rACD), and relative cerebral blood volume (rCBV) and compared these to age-/gender-matched patients with localized glioblastoma. RESULTS: Overall, 16 patients (median age 59.5 years, 4 male) were included in the study. Of these, 8 patients had a glioblastoma with GC growth pattern, and 8 a classical localized growth pattern. While the median rADC (1.27 [IQR 1.12-1.41]) within the T2 lesion was significant lower in glioblastoma with GC growth pattern compared to localized glioblastoma (1.74 [IQR 1.45-1.96]; p = 0.003), the median T2 lesion volume and rCBV within the T2 lesion did not differ significantly. Furthermore, six patients with glioblastoma with GC growth pattern showed focal areas with significantly reduced rADC (p = 0.043), and/or increased rCBV (p = 0.028). CONCLUSIONS: Lower rADC in glioblastoma with GC growth pattern might reflect the diffuse tumor cell infiltration whereas focal areas with decreased rADC and/or increased rCBV probably indicate high tumor cell density and/or abnormal tumor vessels which may be useful for biopsy guidance.

Assessment of collateral blood flow in patients with distal branch occlusion of the middle cerebral artery.

PURPOSE: Aim of this study was to evaluate the collateral blood flow between more distal branches of the middle cerebral artery (MCA) in the case of peripheral MCA branch occlusion on dynamic 4D angiograms. We sought to individually predict the finally resulting infarction volume with regard to the extent of collateral blood flow. METHODS: Overall, 35 acute ischemic stroke patients with peripheral MCA branch occlusion were included. Volumes of the ischemic infarctions and perfusion deficits were measured on diffusion-weighted images DWI and time-to-peak TTP (> 4 s). Collateral flow on 4D MR angiograms were classified as previously specified. RESULTS: On DWI, the ischemic lesions had a mean volume of 3.4 ± 15.1 mL while the mean volume on TTP (> 4 s) was significantly larger 22.0 ± 18.1 mL (P < 0.001). On dynamic 4D angiograms we observed grade 1 in 8 (22.9%), grade 2 in 4 (11.4%), grade 3 in 10 (28.6%), and grade 4 in 13 (37.1%) patients. In comparison to patients with better collateralization (grade 3-4) patients with less sufficient collateralization (grade 0-2) demonstrated larger infarction volumes on initial (11.1 mL (IQR 2.9-35.5) vs. 2.1 mL (IQR 0.5-4.5), P = 0.03) and follow-up DWI (15.5 mL (IQR 12.6-23.3) vs. 1.9 mL (IQR 0.5-4.5), P = 0.03) with prominent infarction growth (7.4 mL (IQR 2.6-10.1) vs. 0.9 mL (IQR 0.2-2.6), P = 0.08). CONCLUSIONS: In the majority of cases with distal MCA branch occlusion a good collateral blood flow has been observed. Nevertheless, in approximately one quarter of patients an insufficient collateral blood flow has been detected that was associated with substantial infarction growth.

Incidence, Locations, and Longitudinal Course of Cerebral Microbleeds in European Moyamoya.

BACKGROUND AND PURPOSE: Cerebral microbleeds (cMBs) have previously been linked with especially high incidence in Asian patients with moyamoya together with high tendency to bleed. This, presumably, is characteristic of patients with moyamoya. Herein, we, therefore, investigate retrospectively the frequency, location, and longitudinal course of cMBs in a large German cohort. METHODS: We included all patients with moyamoya who underwent standard magnetic resonance imaging, including T2*-weighted images, in our department between 1998 and 2015. Two independent readers evaluated magnetic resonance imaging scans to determine the occurrence of cMBs according to the Brain Observer Microbleed Scale. Demographics, initial symptoms leading to hospitalization, and associated diseases were obtained by chart review. RESULTS: Overall, there was a total of 242 T2* studies of 101 included moyamoya patients available with a strong female predominance (69.3%). Eight patients (7.9%) were ≤18 years of age. We detected 25 cMBs within 13 patients (12.9%). One patient <18 of age was presented with a cMB; 2 of 3 patients with an intracranial hemorrhage as initial event demonstrated cMB(s). In 72 of 101 cases, there were 1719 person months of follow-up, with 3 adult patients showing 3 de novo cMBs in the course. The majority of cMBs (64.0%) were located at the cortex/gray-white junction. CONCLUSIONS: Although the frequency of cMBs herein is much higher than the expected age-specific incidence, it is still much lower compared with previous reports on cMBs in moyamoya patients of Asian descent. These results might reflect another ethnic-specific difference in patients diagnosed with moyamoya.

Late-onset major depression is associated with age-related white matter lesions in the brainstem.

OBJECTIVE: Age-related white matter lesions (ARWMLs) have been identified in various clinical conditions such as reduced gait speed, cognitive impairment, urogenital dysfunction, and mood disturbances. Previous studies indicated an association between ARWML and late-onset major depression. However, most of these focused on the extent of supratentorial ARWML and neglected presence and degree of infratentorial lesions. METHODS: In 45 patients (mean age 73.7 ± 6.3 years, 17 (37.8%) men, 28 (62.2%) women) with late-onset major depression, MRI findings (3.0-T MR system, Magnetom Trio, Siemens Medical Systems, Erlangen, Germany) were analyzed with emphasis on the extent of supratentorial and infratentorial, as well as brainstem ARWMLs, and compared with control subjects. ARWMLs were determined by semiquantitative rating scales (modified Fazekas rating scale, Scheltens' rating scale), as well as a semiautomatic volumetric assessment, using a specific software (MRIcron). Supratentorial and infratentorial, as well as brainstem ARWMLs, were assessed both on fluid attenuated inversion recovery and T2-weighted images. RESULTS: Patients with late-onset major depression had significantly higher infratentorial ARWML rating scores (5 (5-7) vs 4.5 (3-6), p = 0.003) on T2-weighted images and volumes (1.58 ± 1.35 mL vs 1.05 ± 0.81 mL, p = 0.03) on T2-weighted images, as well as fluid attenuated inversion recovery images (2.07 ± 1.35 mL vs 1.52 ± 1.10 mL, p = 0.04), than normal controls. In more detail, in particular, the pontine ARWML rating subscore was significantly higher in patients with late-onset major depression (1 (1-2) vs 1 (1-1), p = 0.004). CONCLUSIONS: The extent and localization of brainstem ARWML might be of importance for the pathophysiology of late-onset major depression. In particular, this may hold true for pontine ARWML. Copyright © 2016 John Wiley & Sons, Ltd.

Missing relationship of moyamoya and persistent primitive artery in Europeans. Another distinctive feature or artifact?

PURPOSE: Previous studies found higher incidence of persistent primitive arteries in Asian moyamoya (MM) patients than in the general population, which was thought to be a characteristic trait of the MM entity in general. We analyzed incidence of persistent primitive arteries and demographics of patients with European MM treated in one single center. First, we compared our large dataset to existing literature and second, we raised the question whether European MM demonstrates similar high prevalence of persistent primitive arteries as it was previously presented within Asian MM. METHODS: All European MM on whom revascularization surgery was performed from 1999 to 2013 were included. Demographics and associated diseases were obtained by retrospective chart review. Two independent readers evaluated 122 MM angiograms to determine the occurrence of persistent primitive arteries as well as the Suzuki score. RESULTS: We identified 112 cases with MM disease, 10 with MM syndrome. Mean age at time of diagnosis was 38.2 (range 6-64 years); a peak incidence in early childhood was not observed. Ninety (73.8%) were women, associated systemic diseases were found in four patients. Seven cases (5.7%) presented with unilaterally affected vessels. The majority of patients (71; 58.2%) were graded Suzuki Score 3. One 14-year-old boy with moyamoya presented with a primitive trigeminal artery (0.89%). CONCLUSIONS: We did not find a bimodal age distribution, but only a second peak during adulthood. Unlike previous studies on Asian moyamoya patients, our collective does not exhibit a higher prevalence of persistent primitive arteries than the normal population.

Perfusion patterns in migraine with aura.

OBJECTIVES: Migraine with aura is a common neurological disorder, and differentiation from transient ischemic attack or stroke based on clinical symptoms may be difficult. METHODS: From an MRI report database we identified 33 patients with migraine with aura and compared these to 33 age-matched ischemic stroke patients regarding perfusion patterns on perfusion-weighted imaging (PWI)-derived maps: time to peak (TTP), mean transit time (MTT), and cerebral blood flow and volume (CBF, CBV). RESULTS: In 18/33 (54.5%) patients with migraine with aura, TTP showed areas of hypoperfusion, most of these not limited to the territory of a specific artery but affecting two or more vascular territories. In patients with migraine with aura, TTP (1.09 ± 0.05 vs. 1.47 ± 0.40, p < 0.001) and MTT ratios (1.01 ± 0.10 vs. 1.19 ± 0.21, p = 0.003) were significantly lower compared to patients with ischemic stroke. In contrast to this, CBF and CBV ratios did not differ significantly between both groups. CONCLUSIONS: Migraine aura is usually associated with a perfusion deficit not limited to a specific vascular territory, and only a moderate increase of TTP. Thus, hypoperfusion restricted to a single vascular territory in combination with a marked increase of TTP or MTT may be regarded as atypical for migraine aura and suggestive of acute ischemic stroke.

FLAIR vascular hyperintensities and dynamic 4D angiograms for the estimation of collateral blood flow in posterior circulation occlusion.

INTRODUCTION: The objectives of this paper are to assess collateral blood flow in posterior circulation occlusion by MRI-based approaches (fluid-attenuated inversion recovery (FLAIR) vascular hyperintensities (FVHs), collateralization on dynamic 4D angiograms) and investigate its relation to ischemic lesion size and growth. METHODS: In 28 patients with posterior cerebral artery (PCA) and 10 patients with basilar artery (BA) occlusion, MRI findings were analyzed, with emphasis on distal FVH and collateralization on dynamic 4D angiograms. RESULTS: In PCA occlusion, distal FVH was observed in 18/29 (62.1%), in BA occlusion, in 8/10 (80%) cases. Collateralization on dynamic 4D angiograms was graded 1 in 8 (27.6%) patients, 2 in 1 (3.4%) patient, 3 in 12 (41.4%) patients, and 4 in 8 (27.6%) patients with PCA occlusion and 0 in 1 (10%) patient, 2 in 3 (30%) patients, 3 in 1 (10%) patient, and 4 in 5 (50%) patients with BA occlusion. FVH grade showed neither correlation with initial or follow-up diffusion-weighted image (DWI) lesion size nor DWI-perfusion-weighted imaging (PWI) mismatch ratio. Collateralization on dynamic 4D angiograms correlated inversely with initial DWI lesion size and moderately with the DWI-(PWI) mismatch ratio. The combination of distal FVH and collateralization grade on dynamic 4D angiograms correlated inversely with initial as well as follow-up DWI lesion size and highly with the DWI-PWI mismatch ratio. CONCLUSIONS: In posterior circulation occlusion, FVH is a frequent finding, but its prognostic value is limited. Dynamic 4D angiograms are advantageous to examine and graduate collateral blood flow. The combination of both parameters results in an improved characterization of collateral blood flow and might have prognostic relevance.

Diffusion Restricted Lesions in the Splenium of the Corpus Callosum.

BACKGROUND/AIM: Various neurological disorders are associated with lesions predominantly or exclusively affecting the splenium of the corpus callosum (CC), such as Marchiafava-Bignami syndrome (MBS), reversible splenium lesion (RSL), and ischemic stroke (IS). The spectrum of symptoms is broad and clinical presentations may be indistinguishable. Therefore, we aimed to investigate the additional value of diffusion-weighted imaging (DWI) findings of splenial lesions in patients with MBS, RSL, and IS. PATIENTS AND METHODS: Overall, 23 patients (4 patients with MBS, 10 patients with RSL, and 9 patients with isolated IS in the splenium) were identified from a magnetic resonance imaging report database and analyzed with focus on lesion localization, shape, and size on DWI, as well as relative apparent diffusion coefficient (ADC). RESULTS: A focal hyperintensity in the splenium was observed on DWI in all patients. In MBS symmetrical boomerang-shaped lesions, in RSL central oval or round lesions, and in IS eccentric irregular lesions in the splenium were found. The median lesion size in MBS [6.25 (IQR=2.04-8.62) ml] was significantly larger than that in RSL [0.38 (IQR=0.09-0.92) ml, p=0.01], and in IS [0.09 (IQR=0.05-0.94) ml; p=0.01]. Regarding relative ADC values, no significant differences between MBS [0.32 (IQR=0.19-0.62)], RSL [0.22 (IQR=0.14-0.30)], and IS [0.27 (IQR=0.20-1.19)] were found. CONCLUSION: Diffusion restricted lesions in the splenium of the CC are best classified by localization, shape, and size, whereas relative ADC values are of limited value for differentiation of different neurological disorders.

Transient global amnesia with unexpected clinical and radiological findings: A case series and systematic review.

BACKGROUND: Transient global amnesia (TGA) represents a benign neurological syndrome of unknown pathophysiology, often accompanied by vanishing hippocampal punctate diffusion-weighted imaging lesions (HPDL). The literature suggests that TGA may present with unusual features. This study analyses atypical clinical and radiological manifestations of patients with TGA and/or HPDL. METHODS: We retrospectively reviewed patients with atypical clinical or radiological presentations of TGA and/or HPDL in three neurology centers. We also performed a systematic review of literature using predefined search terms. Results were classified as: A) Atypical clinical manifestations of TGA (such as amnesia with additional manifestations, or only non-amnesic manifestations); B) Atypical radiological manifestations of clinically typical TGA. RESULTS: We identified 83 patients: 18 in our centres (median age 63.5 years, 39% female) and 65 in the literature. In group A, 43 patients presented atypical clinical manifestations such as TGA with added transitory cognitive or sensory-motor deficits, seizures, headaches, but also non-amnesic presentations associated with HPDL and incidental HPDL without symptoms. In group B, 40 patients with typical clinical TGA showed extra-hippocampal punctate diffusion lesions (E-HPDL) which disappeared on follow-up imaging. Using clinical and radiological manifestations, we classified these patients into different categories describing a "TGA-PDL spectrum". CONCLUSIONS: TGA may have atypical clinical manifestations despite typical neuroimaging and patients with typical TGA may show vanishing extra-hippocampal punctate diffusion lesions. TGA, related clinical manifestations, and vanishing punctate diffusion lesions should be considered part of a larger "TGA-PDL spectrum", allowing for better diagnosis of typical and atypical cases and stimulating further studies.

Cerebral network disruption as a possible mechanism for impaired recovery after acute pontine stroke.

BACKGROUND: Recovery from stroke is presumed to be a function of a widespread cerebral network. Chronic white matter lesions (WML) have been proposed to be a predictor of poor outcome after acute stroke. We tested the hypothesis that the extent of WML has an effect on functional recovery in acute pontine stroke by disrupting the integrity of the supratentorial cerebral network. METHODS: Seventeen patients with acute unilateral pontine stroke who had received a standardized stroke workup and additional diffusion tensor imaging (DTI) were studied. After grading the extent of WML according to the Fazekas scale and semiautomated lesion volume calculation, we compared patients with acute pontine infarction and advanced WML to those with absent or minimal WML regarding baseline characteristics, stroke subtype and clinical outcome. In addition, we used tract-based spatial statistics for voxel-wise analysis of the DTI-derived parameter fractional anisotropy in the white matter tracts. RESULTS: The volume of WML ranged between 0.1 and 42.1 cm³ (mean = 15.9) and was graded as follows: 0 in 5.9%, 1 in 35.3%, 2 in 41.2% and 3 in 17.6%. Both patients with Fazekas grades 2-3 (p = 0.014) as well as those with larger WML volumes (p = 0.037) had severer functional deficits at the 3-month follow-up. White matter tracts displaying a significant decrease in fractional anisotropy values were the corpus callosum, the anterior thalamic radiation and the inferior fronto-occipital fasciculus. CONCLUSIONS: Chronic WML contribute to a less favorable clinical outcome after pontine stroke depending on (1) the extent of pre-existing WML and (2) the degree of disruption of cerebral connectivity as indicated by reduced tissue integrity in the white matter not affected by WML as detected by DTI and tract-based spatial statistics.

Recent advances in magnetic resonance imaging in posterior circulation stroke: implications for diagnosis and prognosis.

OPINION STATEMENT: For some time, posterior circulation stroke has been neglected in diagnostic and therapeutic studies for various reasons, such as minor incidence compared to anterior circulation stroke or anatomical and vascular characteristics. This changed at least partly when the New England Medical Center (NEMC) Posterior Circulation Registry was initiated, and now the number of publications concerning posterior circulation stroke is continuously increasing. Whether the differences outweigh the similarities between posterior and anterior circulation stroke remains open to debate, but both are the subject of intensive investigations. In this article, we review the most recent literature on different MRI techniques, such as diffusion-weighted and diffusion tensor imaging (DWI and DTI), perfusion-weighted imaging (PWI), vascular imaging, and susceptibility weighted imaging (SWI), in posterior circulation stroke and discuss their diagnostic and prognostic impact as well as general implications for acute treatment.

FLAIR Vascular Hyperintensities Indicate Slow Poststenotic Blood Flow in ICA Stenosis.

PURPOSE: Occlusion or significant stenosis of the internal carotid artery (ICA) in the cervical segment is commonly associated with a poststenotic decrease in the downstream blood flow and perfusion. Fluid attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH) are a phenomenon that represents slow arterial blood flow. In this study, we investigated the frequency and extent of FVH in the distal ICA in patients with proximal ICA stenosis. METHODS: We analyzed the magnetic resonance imaging (MRI) findings in 51 patients with a total of 60 cervical ICA stenoses with special focus on the frequency and extent of FVH in the area of the petrous segment of the ICA on FLAIR images and correlated these with Doppler/duplex sonography results. RESULTS: In 46 (76.7%) patients with ICA stenosis, FVH could be detected in the petrous segment of the ICA: in 19 (41.3%) patients a thin hyperintense rim near the vessel wall (grade 1), in 24 (52.2%) patients a strong hyperintense rim near the vessel wall (grade 2), and in 3 (6.5%) patients a hyperintense filling of the entire lumen (grade 3) was observed. The extent of FVH in the ICA in the petrous segment showed a high negative correlation with the poststenotic flow velocity (Spearman correlation, R = -0.75, p < 0.001), and moderate correlation with the degree of ICA stenosis (Spearman correlation, R = 0.51, p< 0.001). CONCLUSION: An FVH in the petrous ICA is commonly seen among patients with steno-occlusive disease in proximal ICA and could therefore be useful to recognize a proximal ICA stenosis even on FLAIR images.

Crossed Cerebellar Diaschisis in Alzheimer's Disease Detected by Arterial Spin-labelling Perfusion MRI.

BACKGROUND: Crossed cerebellar diaschisis (CCD) is a phenomenon with depressed metabolism and hypoperfusion in the cerebellum. Using arterial spin-labelling perfusion weighted magnetic resonance imaging (ASL PWI), we investigated the frequency of CCD in patients with Alzheimer's disease (AD) and differences between patients with and without CCD. PATIENTS AND METHODS: In patients with AD who underwent a standardized magnetic resonance imaging including ASL PWI cerebral blood flow was evaluated in the cerebellum, and brain segmentation/volumetry was performed using mdbrain (mediaire GmbH, Berlin, Germany) and FSL FIRST (Functional Magnetic Resonance Imaging of the Brain Software Library). RESULTS: In total, 65 patients were included, and 22 (33.8%) patients were assessed as being CCD-positive. Patients with CCD had a significantly smaller whole brain volume (862.8±49.9 vs. 893.7±62.7 ml, p=0.049) as well as white matter volume (352.9±28.0 vs. 374.3±30.7, p=0.008) in comparison to patients without CCD. CONCLUSION: It was possible to detect CCD by ASL PWI in approximately one-third of patients with AD and was associated with smaller whole brain and white matter volume.

MRI topography of lesions related to internuclear ophthalmoplegia in patients with multiple sclerosis or ischemic stroke.

BACKGROUND AND PURPOSE: Internuclear ophthalmoplegia is a dysfunction of conjugate eye movements, caused by lesions affecting the medial longitudinal fasciculus (MLF). Multiple sclerosis (MS) and ischemic stroke represent the most common pathophysiologies. While magnetic resonance imaging (MRI) allows for localizing lesions affecting the MLF, comprehensive comparative studies exploring potential different spatial characteristics of lesions affecting the MLF are missing until now. METHODS: We retrospectively investigated MRI examinations of 82 patients (40 patients with MS and 42 patients with ischemic stroke). For lesion localization, the brainstem was segmented into (1) ponto-medullary junction, (2) mid pons, (3) upper pons, and (4) mesencephalon. RESULTS: Corresponding lesions affecting the MLF were observed in 29/40 (72.5%) MS and 38/42 (90.5%) stroke patients. Compared to stroke patients, MS patients had significantly more lesions in multiple locations (P < .001). Stroke patients showed more lesions at the level of the mesencephalon (P < .001), while lesions at the level of the ponto-medullary junction, mid, and upper pons did not statistically differ between the groups. CONCLUSION: Our results demonstrate that multiple lesions affecting the MLF make inflammatory-demyelination due to MS more likely, while lesion localization at the level of the mesencephalon favors ischemia.

Intrinsic photogeneration of long-lived charges in a donor-orthogonal acceptor conjugated polymer.

Efficient charge photogeneration in conjugated polymers typically requires the presence of a second component to act as electron acceptor. Here, we report a novel low band-gap conjugated polymer with a donor/orthogonal acceptor motif: poly-2,6-(4,4-dihexadecyl-4H-cyclopenta [2,1-b:3,4-b']dithiophene)-alt-2,6-spiro [cyclopenta[2,1-b:3,4-b']dithiophene-4,9'-fluorene]-2',7'-dicarbonitrile, referred to as PCPDT-sFCN. The role of the orthogonal acceptor is to spatially isolate the LUMO from the HOMO, allowing for negligible exchange energy between electrons in these orbitals and minimising the energy gap between singlet and triplet charge transfer states. We employ ultrafast and microsecond transient absorption spectroscopy to demonstrate that, even in the absence of a separate electron acceptor, PCPDT-sFCN shows efficient charge photogeneration in both pristine solution and film. This efficient charge generation is a result of an isoenergetic singlet/triplet charge transfer state equilibrium acting as a reservoir for charge carrier formation. Furthermore, clear evidence of enhanced triplet populations, which form in less than 1 ps, is observed. Using group theory, we show that this ultrafast triplet formation is due to highly efficient, quantum mechanically allowed intersystem crossing between the bright, initially photoexcited local singlet state and the triplet charge transfer state. Remarkably, the free charges that form via the charge transfer state are extraordinarily long-lived with millisecond lifetimes, possibly due to the stabilisation imparted by the spatial separation of PCPDT-sFCN's donor and orthogonal acceptor motifs. The efficient generation of long-lived charge carriers in a pristine polymer paves the way for single-material applications such as organic photovoltaics and photodetectors.