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PurposeWe aimed to evaluate the performance of deep learning-based generalization of ultra-low-count amyloid PET/MRI enhancement when applied to studies acquired with different scanning hardware and protocols.MethodsEighty simultaneous [18F]florbetaben PET/MRI studies were acquired, split equally between two sites (site 1: Signa PET/MRI, GE Healthcare, 39 participants, 67 ± 8 years, 23 females; site 2: mMR, Siemens Healthineers, 64 ± 11 years, 23 females) with different MRI protocols. Twenty minutes of list-mode PET data (90–110 min post-injection) were reconstructed as ground-truth. Ultra-low-count data obtained from undersampling by a factor of 100 (site 1) or the first minute of PET acquisition (site 2) were reconstructed for ultra-low-dose/ultra-short-time (1% dose and 5% time, respectively) PET images. A deep convolution neural network was pre-trained with site 1 data and either (A) directly applied or (B) trained further on site 2 data using transfer learning. Networks were also trained from scratch based on (C) site 2 data or (D) all data. Certified physicians determined amyloid uptake (+/−) status for accuracy and scored the image quality. The peak signal-to-noise ratio, structural similarity, and root-mean-squared error were calculated between images and their ground-truth counterparts. Mean regional standardized uptake value ratios (SUVR, reference region: cerebellar cortex) from 37 successful site 2 FreeSurfer segmentations were analyzed.ResultsAll network-synthesized images had reduced noise than their ultra-low-count reconstructions. Quantitatively, image metrics improved the most using method B, where SUVRs had the least variability from the ground-truth and the highest effect size to differentiate between positive and negative images. Method A images had lower accuracy and image quality than other methods; images synthesized from methods B–D scored similarly or better than the ground-truth images.ConclusionsDeep learning can successfully produce diagnostic amyloid PET images from short frame reconstructions. Data bias should be considered when applying pre-trained deep ultra-low-count amyloid PET/MRI networks for generalization.

To generate high-resolution maps of the viscoelastic properties of human brain parenchyma for presurgical quantitative assessment in glioblastoma (GB). Twenty-two GB patients underwent routine presurgical work-up supplemented by additional multifrequency magnetic resonance elastography. Two three-dimensional viscoelastic parameter maps, magnitude |G*|, and phase angle φ of the complex shear modulus were reconstructed by inversion of full wave field data in 2-mm isotropic resolution at seven harmonic drive frequencies ranging from 30 to 60 Hz. Mechanical brain maps confirmed that GB are composed of stiff and soft compartments, resulting in high intratumor heterogeneity. GB could be easily differentiated from healthy reference tissue by their reduced viscous behavior quantified by φ (0.37±0.08 vs. 0.58±0.07). |G*|, which in solids more relates to the material's stiffness, was significantly reduced in GB with a mean value of 1.32±0.26 kPa compared to 1.54±0.27 kPa in healthy tissue (P = 0.001). However, some GB (5 of 22) showed increased stiffness. GB are generally less viscous and softer than healthy brain parenchyma. Unrelated to the morphology-based contrast of standard magnetic resonance imaging, elastography provides an entirely new neuroradiological marker and contrast related to the biomechanical properties of tumors.

Glioblastoma and anaplastic astrocytoma represent the most commonly encountered high-grade-glioma (HGG) in adults. Although both neoplasms are very distinct entities in context of epidemiology, clinical course and prognosis, their appearance in conventional magnetic resonance imaging (MRI) is very similar. In search for additional information aiding the distinction of potentially confusable neoplasms, histogram analysis of apparent diffusion coefficient (ADC) maps recently proved to be auxiliary in a number of entities. Therefore, our present exploratory retrospective study investigated whether ADC histogram profile parameters differ significantly between anaplastic astrocytoma and glioblastoma, reflect the proliferation index Ki-67, or are associated with the prognostic relevant MGMT (methylguanine-DNA methyl-transferase) promotor methylation status. Pre-surgical ADC volumes of 56 HGG patients were analyzed by histogram-profiling. Association between extracted histogram parameters and neuropathology including WHO-grade, Ki-67 expression and MGMT promotor methylation status was investigated due to comparative and correlative statistics. Grade IV gliomas were more heterogeneous than grade III tumors. More specifically, ADCmin and the lowest percentile ADCp10 were significantly lower, whereas ADCmax, ADC standard deviation and Skewness were significantly higher in the glioblastoma group. ADCmin, ADCmax, ADC standard deviation, Kurtosis and Entropy of ADC histogram were significantly correlated with Ki-67 expression. No significant difference could be revealed by comparison of ADC histogram parameters between MGMT promotor methylated and unmethylated HGG. ADC histogram parameters differ significantly between glioblastoma and anaplastic astrocytoma and show distinct associations with the proliferative activity in both HGG. Our results suggest ADC histogram profiling as promising biomarker for differentiation of both, however, further studies with prospective multicenter design are wanted to confirm and further elaborate this hypothesis.

Pre-surgical diffusion weighted imaging (DWI) is increasingly important in the context of thyroid cancer for identification of the optimal treatment strategy. It has exemplarily been shown that DWI at 3T can distinguish undifferentiated from well-differentiated thyroid carcinoma, which has decisive implications for the magnitude of surgery. This study used DWI histogram analysis of whole tumor apparent diffusion coefficient (ADC) maps. The primary aim was to discriminate thyroid carcinomas which had already gained the capacity to metastasize lymphatically from those not yet being able to spread via the lymphatic system. The secondary aim was to reflect prognostically important tumor-biological features like cellularity and proliferative activity with ADC histogram analysis. Fifteen patients with follicular-cell derived thyroid cancer were enrolled. Lymph node status, extent of infiltration of surrounding tissue, and Ki-67 and p53 expression were assessed in these patients. DWI was obtained in a 3T system using b values of 0, 400, and 800 s/mm2. Whole tumor ADC volumes were analyzed using a histogram-based approach. Several ADC parameters showed significant correlations with immunohistopathological parameters. Most importantly, ADC histogram skewness and ADC histogram kurtosis were able to differentiate between nodal negative and nodal positive thyroid carcinoma. Conclusions: histogram analysis of whole ADC tumor volumes has the potential to provide valuable information on tumor biology in thyroid carcinoma. However, further studies are warranted.

To investigate if apparent diffusion coefficient (ADC) values within primary central nervous system lymphoma correlate with cellularity and proliferative activity in corresponding histological samples. 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. 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). 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.

Pulmonary Surfactant reduces surface tension in the terminal airways thus facilitating breathing and contributes to host's innate immunity. Surfactant Proteins (SP) A, B, C and D were recently identified as inherent proteins of the CNS. Aim of the study was to investigate cerebrospinal fluid (CSF) SP levels in hydrocephalus patients compared to normal subjects. CSF SP A-D levels were quantified using commercially available ELISA kits in 126 patients (0-84 years, mean 39 years). 60 patients without CNS pathologies served as a control group. Hydrocephalus patients were separated in aqueductal stenosis (AQS, n = 24), acute hydrocephalus without aqueductal stenosis (acute HC w/o AQS, n = 16) and idiopathic normal pressure hydrocephalus (NPH, n = 20). Furthermore, six patients with pseudotumor cerebri were investigated. SP A-D are present under physiological conditions in human CSF. SP-A is elevated in diseases accompanied by ventricular enlargement (AQS, acute HC w/o AQS) in a significant manner (0.67, 1.21 vs 0.38 ng/ml in control, p<0.001). SP-C is also elevated in hydrocephalic conditions (AQS, acute HC w/o AQS; 0.87, 1.71 vs. 0.48 ng/ml in controls, p<0.001) and in Pseudotumor cerebri (1.26 vs. 0.48 ng/ml in controls, p<0.01). SP-B and SP-D did not show significant alterations. The present study confirms the presence of SPs in human CSF. There are significant changes of SP-A and SP-C levels in diseases affecting brain water circulation and elevation of intracranial pressure. Cause of the alterations, underlying regulatory mechanisms, as well as diagnostic and therapeutic consequences of cerebral SP's requires further thorough investigations.

Background/Objectives: Delayed cerebral ischemia (DCI) after an aneurysmal subarachnoid hemorrhage (aSAH) often presents with bilateral vasospasm and cortical spreading depolarizations. Computer tomography perfusion (CTP) is the prevailing screening method for detecting early changes in the cerebral blood flow. Commonly used CTP thresholds include an rCBF < 30% for the core volume and a Tmax > 6 s for hypoperfused tissue detection in acute ischemic stroke. These stroke algorithm computing thresholds compared to the contralateral hemisphere may or may not apply to detect tissue at risk of DCI. We aimed to quantify the volumetric agreement of three different stroke algorithms compared to the final infarct volumes as the standard. Methods: Furthermore, 123 CTP datasets of 75 patients with aSAH suspicious of DCI were processed using Intellispace Portal (ISP), Cercare Threshold, and Cercare Artificial Intelligence (AI) to calculate the tissue-at-risk (hypoperfused) and non-viable tissue (core) volumes. CT infarct volumes in plain CTs were segmented in the follow-up study by using a 3D slicer. Results: The calculated core volumes corresponded best to the final infarct volumes if DCI-related treatment was performed subsequently. Additional postprocessing improved the calculation of core volumes but overestimated the tissue at risk of hypoperfusion in DCI. Whereas the accuracy of tissue-at-risk prediction accelerated without treatment, underlining the importance of intra-arterial spasmolysis and induced hypertension in the prevention of DCI. Conclusions: Cercare AI and ISP revealed a sensitivity of 100% each, with a serious low specificity of <5% that was independent of treatment. Overall, the Cercare Threshold, applying the commonly used stroke thresholds, performed the best in predicting tissue at risk of hypoperfusion in DCI.

BackgroundFlow diversion (FD) has emerged as superior minimally invasive therapy for cerebral aneurysms. However, aneurysms of small peripheral vessel segments have not yet been adequately treatable. More specifically, currently established devices necessitate large microcatheters which impede atraumatic maneuvering. The Silk Vista Baby (SVB), a novel flow diverter, offers the as yet unique feature of deliverability via a 0.017 inch microcatheter. This study reports our first experience with the SVB in challenging intracranial vessels employing a vessel-specific tailored microcatheter strategy.Materials and methods25 patients (27 aneurysms) were prospectively included. A total of 30 SVBs were employed, predominantly targeting demanding aneurysms of the anterior communicating artery complex. The efficacy of the FD was assessed using two-dimensional vector-based perfusion and conventional digital subtraction angiography (DSA) after implantation and at the first follow-up at 3 months. The first follow-up was available in 22 patients.ResultsAll devices were implanted without technical or clinical complications. Eleven treatments were performed using the recommended Headway 17. In 14 interventions the even more maneuverable Excelsior SL10 was used, which was previously tried and tested for safety ’in vitro’ as an alternative delivery system. Aneurysmal influx was strongly reduced after implantation. All parent vessels remained patent. 17/27 aneurysms were completely occluded at first follow-up (∼2.7 months), 6/27 aneurysms showed decreased influx or delayed washout and one remained unchanged. In three cases follow-up DSAs are remaining.ConclusionsSVB provides enhanced controllability in vulnerable segments beyond the circle of Willis. Smaller variants (2.25 mm and 2.75 mm) can safely be implanted via the superiorly navigable Excelsior SL10. Hence, the SVB represents the next evolutionary step in minimally invasive treatment of cerebral aneurysms.

ABSTRACT Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite refined by DSM-5 diagnostic criteria and a new term for MCI – “mild neurocognitive disorder” (mild NCD) – this diagnosis is still based on clinical criteria. To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63 – 79 years old) were selected from the Leipzig-population-based study of adults (LIFE). Serum S100B levels were increased in mild NCD in comparison to controls (p=0.007). Serum NSE levels were also increased, but remained non-significant after Bonferroni-Holm correction (p=0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r=0.20, p=0.01), independently from age. Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk for development of major NCD.

Objective Deep vein thrombosis (DVT) is discussed as a source of embolism for cerebral ischemia in the presence of patent foramen ovale (PFO). However, previous studies reported varying rates of DVT in stroke patients, and recommendations for screening are lacking. This study aimed to characterize patients with stroke or transient ischemic attack (TIA) and concomitant PFO and explore the rate of DVT and associated parameters. Methods Medical records were screened for patients with stroke or TIA and echocardiographic evidence of PFO. Concomitant DVT was identified according to compression ultrasonography of the lower limbs. A variety of demographic, clinical, and laboratory parameters, the RoPE and Wells scores were compared between patients with and without DVT. Results Three-hundred-thirty-nine patients (mean age 61.2 ± 15.4 years, 61.1% male) with stroke or TIA and PFO, treated between 01/2015 and 12/2020, were identified. Stroke and TIA patients did not differ for demographic and vascular risk factors. DVT was found in 17 cases out of 217 (7.8%) with compression ultrasonography. DVT was associated with a history of DVT, cancer, previous immobilization, calf compression pain, calf circumference difference, and a few laboratory abnormalities, e.g., increased D-dimer. A multivariate regression model with stepwise backward selection identified the Wells score (odds ratio 35.46, 95%-confidence interval 4.71–519.92) as a significant predictor for DVT. Conclusion DVT is present in a relevant proportion of patients with cerebral ischemia and PFO, which needs to be considered for the individual diagnostic workup. The Wells score seems suitable for guiding additional examinations, i.e., compression ultrasonography.