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.

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.

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.

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.

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.

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.

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 in optic neuritis.

BACKGROUND: We investigated the frequency of blood-retina barrier impairment in optic neuritis (ON) using gadolinium leakage in ocular structures (GLOS), a novel imaging marker on contrast enhanced fluid attenuated inversion recovery images (FLAIR). METHODS: In 12 patients with acute ON who underwent repeated MRI the presence of GLOS was noted on contrast-enhanced FLAIR. RESULTS: Bilateral GLOS was observed in 4 (33.3%): in 3 symmetrical, and in 1 asymmetrical. In the latter GLOS was ipsilateral to the ON. CONCLUSIONS: GLOS may be observed frequently in ON. Asymmetrical GLOS may be caused by a more local effect of ON.

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.

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.

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.

Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM).

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE: To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. METHODS: Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. EXPECTED OUTCOMES: We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. DISCUSSION: Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

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.

Objective Comparison Using Guideline-based Query of Conventional Radiological Reports and Structured Reports.

BACKGROUND: This feasibility study of text-mining-based scoring algorithm provides an objective comparison of structured reports (SR) and conventional free-text reports (cFTR) by means of guideline-based key terms. Furthermore, an open-source online version of this ranking algorithm was provided with multilingual text-retrieval pipeline, customizable query and real-time-scoring. MATERIALS AND METHODS: Twenty-five patients with suspected stroke and magnetic resonance imaging were re-assessed by two independent/blinded readers [inexperienced: 3 years; experienced >6 years/Board-certified). SR and cFTR were compared with guideline-query using the cosine similarity score (CSS) and Wilcoxon signed-rank test. RESULTS: All pathological findings (18/18) were identified by SR and cFTR. The impressions section of the SRs of the inexperienced reader had the highest median (0.145) and maximal (0.214) CSS and were rated significantly higher (p=2.21×10-5 and p=1.4×10-4, respectively) than cFTR (median=0.102). CSS was robust to variations of query. CONCLUSION: Objective guideline-based comparison of SRs and cFTRs using the CSS is feasible and provides a scalable quality measure that can facilitate the adoption of structured reports in all fields of radiology.

Susceptibility Vessel Sign on T2*-Weighted Gradient Echo Imaging in Lacunar Infarction.

BACKGROUND/AIM: In stroke due to large vessel occlusion, thrombotic material can be demonstrated by the susceptibility vessel sign (SVS), a hypointense signal on T2*-weighted gradient echo magnetic resonance (GRE) images. In the present study, we evaluated the value of GRE for the detection of perforating artery occlusion in hyperacute lacunar infarction (LI). MATERIALS AND METHODS: The presence of SVS on GRE in 58 patients with LI who underwent magnetic resonance imaging within 24 hours after symptom onset was analyzed. RESULTS: On diffusion-weighted images (DWI), LI was found in the basal ganglia in 17.2%, internal capsule in 25.9%, corona radiata in 19.0%, thalamus in 32.8%, and brainstem in 5.2%. On GRE a subtle circumscribed hypointense signal at the lower edge of the LI consistent with SVS was detected in 11/58 (19%) patients. Patients with SVS had larger ischemic lesions on DWI (p=0.045). CONCLUSION: SVS on GRE may be useful for detection of perforating artery occlusion in a subset of patients with hyperacute LI.

Anatomical distribution of cerebral microbleeds and intracerebral hemorrhage in vertebrobasilar dolichoectasia.

OBJECTIVES: Vertebrobasilar dolichoectasia (VBD) is a dilatative arteriopathy associated with intracerebral hemorrhage. In the present study, we sought to evaluate the frequency and anatomical distribution of cerebral microbleeds (cMBs) and intracerebral hemorrhage (ICH) in VBD. METHODS: From a MRI database 94 VBD patients were identified and analyzed with special emphasis on cMBs and ICH on T2*-weighted gradient echo images (GRE) in relation to the established diagnostic MRI criteria of VBD (diameter, height, and lateral position). cMBs/ICH location was categorized into anterior/posterior circulation. Clinical information like demographic details, clinical symptoms, and comorbidities were abstracted from the case records. An extensive modelling approach using generalized linear mixed-effects models was used. RESULTS: Overall, 79 (84.0%) patients (mean age 72.1±10.0 years, 74.7% male) with a standard stroke MRI protocol including T2*-weighted images were included in the analysis. cMBs were observed in 38/79 (48.1%) patients, ranging from 1 to 84 cMBs per patient. In the posterior circulation cMBs were observed more frequently (34/38 (89.5%)) in comparison to the anterior circulation (24/38 (63.2%)). cMBs were observed in the thalamus in 20/38 (52.6%), hippocampus in 1/38 (2.6%), occipital lobe in 18/38 (47.4%), pons in 6/38 (15.8%), medulla oblongata in 2/38 (5.2%), and cerebellum in 14/38 (36.8%) patients. ICH was observed in only 6/79 (7.6%) patients. There were significantly more cMBs in the posterior- (NCMBs-PC = 1.717, 95%CI: 1.336-2.208, p = 0.0315) than in the anterior circulation. Logistic regression model showed a significant positive effect of clinical symptoms such as ischemic, TIA and hemorrhagic stroke on the presence of cMBs (OR = 3.34, 95%CI [2.0-5.57], p = 0.0184; ndf = 78, AIC = 107.51). General linear model showed that clinical symptoms have a highly significant effect on the number of cMBs (N = 2.78, 95%CI [2.51-3.07], p<2*10-16; ndf = 78, AIC = 1218). CONCLUSION: cMBs and ICH may be observed in the anterior and posterior circulation in VBD but they occur more frequently in the posterior circulation. Most common anatomical locations of cMBs in VBD were the thalamus, occipital lobe and cerebellum. This posterior dominance of cMBs and ICH in VBD might reflect a specific underlying vascular pathology.

Separating Symptomatic Alzheimer's Disease from Depression based on Structural MRI.

Older patients with depression or Alzheimer's disease (AD) at the stage of early dementia or mild cognitive impairment may present with objective cognitive impairment, although the pathology and thus therapy and prognosis differ substantially. In this study, we assessed the potential of an automated algorithm to categorize a test set of 65 T1-weighted structural magnetic resonance images (MRI). A convenience sample of elderly individuals fulfilling clinical criteria of either AD (n = 28) or moderate and severe depression (n = 37) was recruited from different settings to assess the potential of the pattern recognition method to assist in the differential diagnosis of AD versus depression. We found that our algorithm learned discriminative patterns in the subject's grey matter distribution reflected by an area under the receiver operator characteristics curve of up to 0.83 (confidence interval ranged from 0.67 to 0.92) and a balanced accuracy of 0.79 for the separation of depression from AD, evaluated by leave-one-out cross validation. The algorithm also identified consistent structural differences in a clinically more relevant scenario where the data used during training were independent from the data used for evaluation and, critically, which included five possible diagnoses (specifically AD, frontotemporal dementia, Lewy body dementia, depression, and healthy aging). While the output was insufficiently accurate to use it directly as a means for classification when multiple classes are possible, the continuous output computed by the machine learning algorithm differed between the two groups that were investigated. The automated analysis thus could complement, but not replace clinical assessments.