Matthias Gawlitza

Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease

IntroductionCerebral small vessel disease (cSVD) is one of the most prevalent neurological disorders. The progressive remodeling of brain microvessels due to arterial hypertension or other vascular risk factors causes subtle, but constant cognitive decline through to manifest dementia and substantially increases the risk for stroke. Preliminary evidence suggests the contribution of the immune system to disease initiation and progression, but a more detailed understanding is impaired by the unavailability of appropriate animal models. Here, we introduce the spontaneously hypertensive rat (SHR) as a model for early onset cSVD and unveiled substantial immune changes in conjunction with brain abnormalities that resemble clinical findings.ResultsIn contrast to age-matched normotensive Wistar Kyoto (WKY) rats, male SHR exhibited non-spatial memory deficits. Magnetic resonance imaging showed brain atrophy and a reduction of white matter volumes in SHR. Histological analyses confirmed white matter demyelination and unveiled a circumscribed blood brain barrier dysfunction in conjunction with micro- and macrogliosis in deep cortical regions. Flow cytometry and histological analyses further revealed substantial disparities in cerebral CD45high leukocyte counts and distribution patterns between SHR and WKY. SHR showed lower counts of T cells in the choroid plexus and meningeal spaces as well as decreased interleukin-10 levels in the cerebrospinal fluid. On the other hand, both T and NK cells were significantly augmented in the SHR brain microvasculature.ConclusionsOur results indicate that SHR share behavioral and neuropathological characteristics with human cSVD patients and further undergird the relevance of immune responses for the initiation and progression of cSVD.

Flow diversion treatment of complex bifurcation aneurysms beyond the circle of Willis: a single-center series with special emphasis on covered cortical branches and perforating arteries

Background Data regarding anatomic and clinical results of flow diversion treatment in complex bifurcation aneurysms of the anterior circulation are scarce. Objective To present our results of treatment of these lesions with special emphasis on the fate of ‘jailed’ cortical branches and perforating arteries. Methods Seventeen patients were treated with flow diverters (FDs) for 18 aneurysms of the middle cerebral artery bifurcation (n=13) and the anterior communicating artery complex (n=5). Nineteen cortical branches were covered. A single FD was used in all patients. Results At latest follow-up (mean 7.9 months; range 3–36; median 4.0) 2/19 (10.5%) of the covered branches were occluded, 9/19 (47.4%) showed a decreased caliber and the remaining branches were unchanged. All branch modifications were clinically asymptomatic. Mortality and permanent morbidity were 0%. Symptomatic ischemic events in perforator territories occurred in three patients (17.6%), which were reversible in all of them within 24 h. Follow-up MRI disclosed asymptomatic lacunar defects corresponding to covered perforating artery territories in five patients (29.4%). Altogether, perforator lesions—symptomatic and asymptomatic—occurred in 7/17 patients (41.2%). 33.3% of the aneurysms were occluded at latest follow-up; decreased diameters were seen in the other 66.7%. Conclusions Flow diversion of bifurcation aneurysms is feasible with low rates of permanent morbidity and mortality. Caliber reduction and asymptomatic occlusion of covered cortical branches seems to be common, yet ischemic complications are rather linked to perforator occlusions. Our results on aneurysm occlusion rates are preliminary and longer follow-up periods are warranted.

Distance to Thrombus in Acute Middle Cerebral Artery Occlusion A Predictor of Outcome After Intravenous Thrombolysis for Acute Ischemic Stroke

Background and Purpose— In patients with acute middle cerebral artery (MCA) stroke, therapeutic decisions are influenced by the location of the occlusion. This study aimed to analyze clinical outcomes in patients with acute ischemic MCA stroke treated with systemic intravenous thrombolysis (IVT) using recombinant tissue plasminogen activator, according to the location of the occlusion. Methods— Of 621 patients screened, 136 with acute stroke and MCA occlusion confirmed by CT angiography were retrospectively included in this study. The distance from the carotid T to the thrombus (DT) on coronal maximum intensity projection images and the thrombus length were measured. The correlation between DT and the modified Rankin Scale score at 90 days was analyzed. Results— DT was an independent predictor of clinical outcome in stroke patients treated with IVT. A long DT was significantly correlated with a good clinical outcome (modified Rankin Scale score at 90 days ⩽2). A poor clinical outcome was exponentially more likely than a good outcome when the DT was <16 mm (P<0.001). The thrombus length was not correlated with the modified Rankin Scale score at 90 days. A long thrombus (>8 mm) occurred significantly more often in the proximal MCA than the distal MCA (P<0.001). Conclusion— DT is an independent predictor of clinical outcome in patients with acute MCA occlusion treated with IVT. In acute stroke with MCA occlusion confirmed by CT angiography and DT <16 mm, the likelihood of a good clinical outcome after treatment with IVT was exponentially <50%. This might warrant the evaluation of other therapy forms than IVT in patients with proximal MCA occlusion.

Simultaneous 18F-FDG-PET/MRI: Associations between diffusion, glucose metabolism and histopathological parameters in patients with head and neck squamous cell carcinoma

OBJECTIVES To analyze possible associations between functional simultaneous (18)F-FDG-PET/MR imaging parameters and histopathological parameters in head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS 11 patients (2 female, 9 male; mean age 56.0years) with biopsy-proven primary HNSCC underwent simultaneous (18)F-FDG-PET/MRI with a dedicated head and neck protocol including diffusion weighted imaging. For each tumor, glucose metabolism was estimated with standardized uptake values (SUV) and diffusion restriction was calculated using apparent diffusion coefficients (ADC). The tumor proliferation index was estimated on Ki 67 antigen stained specimens. Cell count, total nucleic area, and average nucleic area were estimated in each case. Pearsons correlation coefficient was used to analyze possible associations between the estimated parameters. RESULTS The mean SUVmax value was 24.41±6.51, and SUVmean value 15.01±4.07. Mean values (×10(-3)mm(2)s(-1)) of ADC parameters were as follows: ADCmin: 0.65±0.20; ADCmean: 1.28±0.18; and ADCmax: 2.16±0.35. Histopathological analysis identified the following results: cell count 1069.82±388.66, total nucleic area 150771.09±61177.12μm(2), average nucleic area 142.90±57.27μm(2) and proliferation index 49.09±22.67%. ADCmean correlated with Ki 67 level (r=-0.728, p=0.011) and total nucleic area (r=-0.691, p=0.019) and tended to correlate with average nucleic area (r=-0.527, p=0.096). ADCmax correlated with Ki 67 level (r=-0.633, p=0.036). SUVmax also tended to correlate with average nucleic area (r=0.573, p=0.066). Combined parameter SUVmax/ADCmin correlated with average nucleic area (r=0.627, p=0.039). CONCLUSION ADC and SUV values showed significant correlations with different histopathological parameters and can be used as biological markers in HNSCC.

FLAIR-hyperintense vessel sign, diffusion-perfusion mismatch and infarct growth in acute ischemic stroke without vascular recanalisation therapy

BACKGROUND AND PURPOSE To investigate the relation between DWI-PWI mismatch and FLAIR-hyperintense vessel (FHV) sign and their influence on the prediction of the infarct growth in stroke patients without vessel recanalising therapy. PATIENTS AND METHODS Thirty-three patients with non-lacunar acute stroke and not eligible for recanalisation therapy received cerebral MRI at the day of admission and after 7±1 days. DWI and PWI lesion volumes, DWI-PWI mismatch volumes, infarct growth, relative mismatch and relative infarct growth were assessed. FHV sign was subdivided into (i) proximal or (ii) distal, the latter graded as either (i) prominent or (ii) subtle. RESULTS FHV sign did not predict absolute or relative infarct growth. Significantly larger DWI lesions, PWI lesions and mismatch volumes were observed in FHV-positive infarcts. There were significant correlations between the degree of FHV sign and PWI lesion volume (r=0.52; P<0.01) as well as mismatch volume (r=0.49; P<0.01), whereas FHV sign did not correlate with the initial DWI lesion size (r=0.33; P=0.059). We found a strong correlation between relative DWI-to-PWI mismatch and relative infarct growth (r=0.91; P<0.01) yet no correlation between absolute mismatch volumes and infarct growth was evident (r=0.18, P=0.35). CONCLUSION The FHV sign is associated with larger PWI lesion volumes and DWI-to-PWI mismatch volumes in acute stroke and thus seems to be an indicator of collateral flow. However, it is unsuitable to predict infarct growth. The latter occurred when DWI-to-PWI mismatches were present with bigger relative mismatch volumes making subsequent infarct growth more likely.

In Vivo Correlation of Glucose Metabolism, Cell Density and Microcirculatory Parameters in Patients with Head and Neck Cancer: Initial Results Using Simultaneous PET/MRI

Objective To demonstrate the feasibility of simultaneous acquisition of 18F-FDG-PET, diffusion-weighted imaging (DWI) and T1-weighted dynamic contrast-enhanced MRI (T1w-DCE) in an integrated simultaneous PET/MRI in patients with head and neck squamous cell cancer (HNSCC) and to investigate possible correlations between these parameters. Methods 17 patients that had given informed consent (15 male, 2 female) with biopsy-proven HNSCC underwent simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE. SUVmax, SUVmean, ADCmean, ADCmin and K trans, k ep and v e were measured for each tumour and correlated using Spearman’s ρ. Results Significant correlations were observed between SUVmean and K trans (ρ = 0.43; p ≤ 0.05); SUVmean and k ep (ρ = 0.44; p ≤ 0.05); K trans and k ep (ρ = 0.53; p ≤ 0.05); and between k ep and v e (ρ = -0.74; p ≤ 0.01). There was a trend towards statistical significance when correlating SUVmax and ADCmin (ρ = -0.35; p = 0.08); SUVmax and K trans (ρ = 0.37; p = 0.07); SUVmax and k ep (ρ = 0.39; p = 0.06); and ADCmean and v e (ρ = 0.4; p = 0.06). Conclusion Simultaneous 18F-FDG-PET/MRI including DWI and T1w-DCE in patients with HNSCC is feasible and allows depiction of complex interactions between glucose metabolism, microcirculatory parameters and cellular density.

Diffusion-weighted MRI reflects proliferative activity in primary CNS lymphoma

Purpose To investigate if apparent diffusion coefficient (ADC) values within primary central nervous system lymphoma correlate with cellularity and proliferative activity in corresponding histological samples. Materials and Methods Echo-planar diffusion-weighted magnetic resonance images obtained from 21 patients with primary central nervous system lymphoma were reviewed retrospectively. Regions of interest were drawn on ADC maps corresponding to the contrast enhancing parts of the tumors. Biopsies from all 21 patients were histologically analyzed. Nuclei count, total nuclei area and average nuclei area were measured. The proliferation index was estimated as Ki-67 positive nuclei divided by total number of nuclei. Correlations of ADC values and histopathologic parameters were determined statistically. Results Ki-67 staining revealed a statistically significant correlation with ADCmin (r = -0.454, p = 0.038), ADCmean (r = -0.546, p = 0.010) and ADCmax (r = -0.515, p = 0.017). Furthermore, ADCmean correlated in a statistically significant manner with total nucleic area (r = -0.500, p = 0.021). Conclusion Low ADCmin, ADCmean and ADCmax values reflect a high proliferative activity of primary cental nervous system lymphoma. Low ADCmean values—in concordance with several previously published studies—indicate an increased cellularity within the tumor.

Interactive Volumetry Of Liver Ablation Zones.

Percutaneous radiofrequency ablation (RFA) is a minimally invasive technique that destroys cancer cells by heat. The heat results from focusing energy in the radiofrequency spectrum through a needle. Amongst others, this can enable the treatment of patients who are not eligible for an open surgery. However, the possibility of recurrent liver cancer due to incomplete ablation of the tumor makes post-interventional monitoring via regular follow-up scans mandatory. These scans have to be carefully inspected for any conspicuousness. Within this study, the RF ablation zones from twelve post-interventional CT acquisitions have been segmented semi-automatically to support the visual inspection. An interactive, graph-based contouring approach, which prefers spherically shaped regions, has been applied. For the quantitative and qualitative analysis of the algorithm’s results, manual slice-by-slice segmentations produced by clinical experts have been used as the gold standard (which have also been compared among each other). As evaluation metric for the statistical validation, the Dice Similarity Coefficient (DSC) has been calculated. The results show that the proposed tool provides lesion segmentation with sufficient accuracy much faster than manual segmentation. The visual feedback and interactivity make the proposed tool well suitable for the clinical workflow.

Imaging Follow-Up of Intracranial Aneurysms Treated by Endovascular Means: Why, When, and How?

Aneurysm treatment is dedicated to prevention of rupture (for unruptured aneurysms) or rebleeding (for ruptured aneurysms). Endovascular embolization has become the first-line treatment for intracranial aneurysms in the majority of cases in many institutions. This minimally invasive approach achieved lower morbidity and mortality rates when compared with surgical management.1–4 However, although successful in improving patient care, its durability has been noted to be its Achilles’ heel since the earliest application of this technology. Indeed, after endovascular treatment (EVT) ≈20% of patients will experience aneurysm or neck reopening after traditional endovascular coiling, necessitating retreatment in about half of them to maintain long-term protection over bleeding.5 Despite this issue, low rates of bleeding have been reported after EVT of ruptured aneurysms, and its clinical superiority over surgery seems to be maintained over time according to the long-term clinical follow-up of the International Subarachnoid Aneurysm Trial (ISAT) cohort.6,7 In the Cerebral Aneurysm Rerupture after Treatment (CARAT) study, the bleeding rate after coil embolization was 0.11% (mean follow-up time, 4.4 years), whereas in the International Subarachnoid Aneurysm Trial, the annual risk of bleeding after coil-treated aneurysms was 0.08%.8 In a large single-center study, the Barrow Ruptured Aneurysm Trial (BRAT), no bleeding was observed after 6 years in the coiling arm, but 4.6% of these patients were retreated.9 Thus, one may question the clinical usefulness of performing imaging follow-up, balancing the small risk of bleeding after EVT with the cost-effectiveness of follow-up. Although the primary end points of these studies were clinical, it is important to note that the majority of EVT patients had imaging follow-up performed at the discretion of the treating physician. For example, in the ISAT trial, 88.2% of the patients in the EVT arm (881 patients) had follow-up angiograms, generally performed 6 …

Correlations Between DCE MRI and Histopathological Parameters in Head and Neck Squamous Cell Carcinoma

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) can characterize perfusion and vascularization of tissues. DCE MRI parameters can differentiate between malignant and benign lesions and predict tumor grading. The purpose of this study was to correlate DCE MRI findings and various histopathological parameters in head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Sixteen patients with histologically proven HNSCC (11 cases primary tumors and in 5 patients with local tumor recurrence) were included in the study. DCE imaging was performed in all cases and the following parameters were estimated: Ktrans, Ve, Kep, and iAUC. The tumor proliferation index was estimated on Ki 67 antigen stained specimens. Microvessel density parameters (stained vessel area, total vessel area, number of vessels, and mean vessel diameter) were estimated on CD31 antigen stained specimens. Spearmans non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. RESULTS: The mean values of DCE perfusion parameters were as follows: Ktrans 0.189 ± 0.056 min−1, Kep 0.390 ± 0.160 min−1, Ve 0.548 ± 0.119%, and iAUC 22.40 ± 12.57. Significant correlations were observed between Kep and stained vessel areas (r = 0.51, P = .041) and total vessel areas (r = 0.5118, P = .043); between Ve and mean vessel diameter (r = −0.59, P = .017). Cell count had a tendency to correlate with Ve (r = −0.48, P = .058). In an analysis of the primary HNSCC only, a significant inverse correlation between Ktrans and KI 67 was identified (r = −0.62, P = .041). Our analysis showed significant correlations between DCE parameters and histopathological findings in HNSCC.