| 41. |
- Durmo, Faris, et al.
(author)
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Assessment of Amide proton transfer weighted (APTw) MRI for pre-surgical prediction of final diagnosis in gliomas
- 2020
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12
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Journal article (peer-reviewed)abstract
- PURPOSE: Radiological assessment of primary brain neoplasms, both high (HGG) and low grade tumors (LGG), based on contrast-enhancement alone can be inaccurate. We evaluated the radiological value of amide proton transfer weighted (APTw) MRI as an imaging complement for pre-surgical radiological diagnosis of brain tumors.METHODS: Twenty-six patients were evaluated prospectively; (22 males, 4 females, mean age 55 years, range 26-76 years) underwent MRI at 3T using T1-MPRAGE pre- and post-contrast administration, conventional T2w, FLAIR, and APTw imaging pre-surgically for suspected primary/secondary brain tumor. Assessment of the additional value of APTw imaging compared to conventional MRI for correct pre-surgical brain tumor diagnosis. The initial radiological pre-operative diagnosis was based on the conventional contrast-enhanced MR images. The range, minimum, maximum, and mean APTw signals were evaluated. Conventional normality testing was performed; with boxplots/outliers/skewness/kurtosis and a Shapiro-Wilk's test. Mann-Whitney U for analysis of significance for mean/max/min and range APTw signal. A logistic regression model was constructed for mean, max, range and Receiver Operating Characteristic (ROC) curves calculated for individual and combined APTw signals.RESULTS: Conventional radiological diagnosis prior to surgery/biopsy was HGG (8 patients), LGG (12 patients), and metastasis (6 patients). Using the mean and maximum: APTw signal would have changed the pre-operative evaluation the diagnosis in 8 of 22 patients (two LGGs excluded, two METs excluded). Using a cut off value of >2.0% for mean APTw signal integral, 4 of the 12 radiologically suspected LGG would have been diagnosed as high grade glioma, which was confirmed by histopathological diagnosis. APTw mean of >2.0% and max >2.48% outperformed four separate clinical radiological assessments of tumor type, P-values = .004 and = .002, respectively.CONCLUSIONS: Using APTw-images as part of the daily clinical pre-operative radiological evaluation may improve diagnostic precision in differentiating LGGs from HGGs, with potential improvement of patient management and treatment.
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| 42. |
- Durmo, Faris, et al.
(author)
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Brain Tumor Characterization Using Multibiometric Evaluation of MRI
- 2018
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In: Tomography : a journal for imaging research. - : MDPI AG. - 2379-1381. ; 4:1, s. 14-25
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Journal article (peer-reviewed)abstract
- The aim was to evaluate volume, diffusion, and perfusion metrics for better presurgical differentiation between high-grade gliomas (HGG), low-grade gliomas (LGG), and metastases (MET). For this retrospective study, 43 patients with histologically verified intracranial HGG (n = 18), LGG (n = 10), and MET (n = 15) were chosen. Preoperative magnetic resonance data included pre- and post-gadolinium contrast-enhanced T1-weighted fluid-attenuated inversion recover, cerebral blood flow (CBF), cerebral blood volume (CBV), fractional anisotropy, and apparent diffusion coefficient maps used for quantification of magnetic resonance biometrics by manual delineation of regions of interest. A binary logistic regression model was applied for multiparametric analysis and receiver operating characteristic (ROC) analysis. Statistically significant differences were found for normalized-ADC-tumor (nADC-T), normalized-CBF-tumor (nCBF-T), normalized-CBV-tumor (nCBV-T), and normalized-CBF-edema (nCBF-E) between LGG and HGG, and when these metrics were combined, HGG could be distinguished from LGG with a sensitivity and specificity of 100%. The only metric to distinguish HGG from MET was the normalized-ADC-E with a sensitivity of 68.8% and a specificity of 80%. LGG can be distinguished from MET by combining edema volume (Vol-E), Vol-E/tumor volume (Vol-T), nADC-T, nCBF-T, nCBV-T, and nADC-E with a sensitivity of 93.3% and a specificity of 100%. The present study confirms the usability of a multibiometric approach including volume, perfusion, and diffusion metrics in differentially diagnosing brain tumors in preoperative patients and adds to the growing body of evidence in the clinical field in need of validation and standardization.
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| 43. |
- Durmo, Faris, et al.
(author)
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Multivoxel 1H-MR Spectroscopy Biometrics for Preoprerative Differentiation Between Brain Tumors
- 2018
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In: Tomography : a journal for imaging research. - : MDPI AG. - 2379-1381. ; 4:4, s. 172-181
-
Journal article (peer-reviewed)abstract
- We investigated multivoxel proton magnetic resonance spectroscopy (1H-MRS) biometrics for preoperative differentiation and prognosis of patients with brain metastases (MET), low-grade glioma (LGG) and high-grade glioma (HGG). In total, 33 patients (HGG, 14; LGG, 9; and 10 MET) were included. 1H-MRS imaging (MRSI) data were assessed and neurochemical profiles for metabolites N-acetyl aspartate (NAA) + NAAG(NAA), Cr + PCr(total creatine, tCr), Glu + Gln(Glx), lactate (Lac), myo-inositol(Ins), GPC + PCho(total choline, tCho), and total lipids, and macromolecule (tMM) signals were estimated. Metabolites were reported as absolute concentrations or ratios to tCho or tCr levels. Voxels of interest in an MRSI matrix were labeled according to tissue. Logistic regression, receiver operating characteristic, and Kaplan-Meier survival analysis was performed. Across HGG, LGG, and MET, average Ins/tCho was shown to be prognostic for overall survival (OS): low values (≤1.29) in affected hemisphere predicting worse OS than high values (>1.29), (log rank < 0.007). Lip/tCho and Ins/tCho combined showed 100% sensitivity and specificity for both HGG/LGG (P < .001) and LGG/MET (P < .001) measured in nonenhancing/contrast-enhancing lesional tissue. Combining tCr/tCho in perilesional edema with tCho/tCr and NAA/tCho from ipsilateral normal- appearing tissue yielded 100% sensitivity and 81.8% specificity (P < .002) for HGG/MET. Best single biomarker: Ins/tCho for HGG/LGG and total lipid/tCho for LGG/MET showed 100% sensitivity and 75% and 100% specificity, respectively. HGG/MET; NAA/tCho showed 75% sensitivity and 84.6% specificity. Multivoxel 1H-MRSI provides prognostic information for OS for HGG/LGG/MET and a multibiometric approach for differentiation may equal or outperform single biometrics.
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| 44. |
- Eckermann, Marina, et al.
(author)
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3d phase-contrast nanotomography of unstained human skin biopsies may identify morphological differences in the dermis and epidermis between subjects
- 2021
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In: Skin Research and Technology. - : Wiley. - 0909-752X .- 1600-0846. ; 27:3, s. 316-323
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Journal article (peer-reviewed)abstract
- Background: Enteric neuropathy is described in most patients with gastrointestinal dysmotility and may be found together with reduced intraepidermal nerve fiber density (IENFD). The aim of this pilot study was to assess whether three-dimensional (3d) imaging of skin biopsies could be used to examine various tissue components in patients with gastrointestinal dysmotility. Material and methods: Four dysmotility patients of different etiology and two healthy volunteers were included. From each subject, two 3-mm punch skin biopsies were stained with antibodies against protein gene product 9.5 or evaluated as a whole with two X-ray phase-contrast computed tomography (CT) setups, a laboratory µCT setup and a dedicated synchrotron radiation nanoCT end-station. Results: Two patients had reduced IENFD, and two normal IENFD, compared with controls. µCT and X-ray phase-contrast holographic nanotomography scanned whole tissue specimens, with optional high-resolution scans revealing delicate structures, without differentiation of various fibers and cells. Irregular architecture of dermal fibers was observed in the patient with Ehlers-Danlos syndrome and the patient with idiopathic dysmotility showed an abundance of mesenchymal ground substance. Conclusions: 3d phase-contrast tomographic imaging may be useful to illustrate traits of connective tissue dysfunction in various organs and to demonstrate whether disorganized dermal fibers could explain organ dysfunction.
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| 45. |
- Ek Olofsson, Henric, et al.
(author)
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Are cortical microvascular raspberries caused by cerebral hypoperfusion? An exploratory pathological study
- 2021
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In: Cerebral Circulation - Cognition and Behavior. - : Elsevier BV. - 2666-2450. ; 2
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Journal article (peer-reviewed)abstract
- Introduction: This retrospective study investigated a cortical microvascular formation, termed a ‘raspberry’ due to its appearance under a bright-field microscope. We examined whether there is support for the hypothesis that raspberry formation is an angiogenic process induced by cerebral hypoperfusion. Materials and Methods: Raspberries were manually quantified in haematoxylin and eosin-stained cortical sections from the anterior frontal lobe of deceased individuals who had undergone a diagnostic neuropathological examination at the Department of Pathology, Lund, Sweden, during April 2019–January 2021. Subjects represented consecutively received cases during this 22-month period. The raspberry density was compared between subjects according to variables collected from medical records and autopsy reports: age, sex, hypertension, diabetes mellitus, atrial fibrillation, orthostatic hypotension, chronic heart failure, acute circulatory failure, aortic atherosclerosis, atherosclerosis of the basal cerebral arteries (referred to as ‘cerebral atherosclerosis’), cerebral small vessel disease, cerebral amyloid angiopathy, cerebral infarction, and ischaemic white matter disease. Results: 62 subjects were included. The mean age was 71.9 years (range 46–97 years). 21 subjects (33.9%) were female. Independent-samples t-test showed a higher raspberry density in subjects with cerebral atherosclerosis (p = 0.029; 95% CI 0.7, 11.6 raspberries/cm²). The higher raspberry density in subjects with cerebral atherosclerosis remained in multiple linear regression (p = 0.003; 95% CI 2.3, 11.1 raspberries/cm²). Conclusion: This exploratory study indicates that cortical raspberries could be associated with cerebral atherosclerosis. The remaining results were inconclusive but motivate further examination of variables such as acute circulatory failure.
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| 46. |
- Ek Olofsson, Henric, et al.
(author)
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Cortical microvascular raspberries and ageing : an independent but not exclusive relationship
- 2023
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In: Acta Neuropathologica Communications. - 2051-5960. ; 11
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Journal article (peer-reviewed)abstract
- Introduction: Raspberries are cerebral microvascular formations of unknown origin, defined as three or more transversally sectioned vascular lumina surrounded by a common perivascular space. We have previously demonstrated an increased raspberry density in the cortex of patients with vascular dementia and cerebral atherosclerosis, while studies by other authors on overlapping and synonymously defined vascular entities mainly associate them with advancing age. The aim of the present study was to examine the relationship between raspberries and age in a large study sample while including multiple potential confounding factors in the analysis.Materials and methods: Our study sample consisted of 263 individuals aged 20–97 years who had undergone a clinical autopsy including a neuropathological examination. The cortical raspberry density had either been quantified as part of a previous study or was examined de novo in a uniform manner on haematoxylin- and eosin-stained tissue sections from the frontal lobe. The medical records and autopsy reports were assessed regarding neurodegeneration, cerebral infarcts, cerebral atherosclerosis and small vessel disease, cardiac hypertrophy, nephrosclerosis, hypertension, and diabetes mellitus. With the patients grouped according to 10-year age interval, non-parametric tests (the Kruskal–Wallis test, followed by pairwise testing with Bonferroni-corrected P values) and multiple linear regression models (not corrected for multiple tests) were performed.Results: The average raspberry density increased with advancing age. The non-parametric tests demonstrated statistically significant differences in raspberry density when comparing the groups aged 60–99 years and 70–99 years to those aged 20–29 years (P < 0.012) and 30–59 years (P < 0.011), respectively. The multiple linear regression models demonstrated positive associations with age interval (P < 0.001), cerebral atherosclerosis (P = 0.024), cardiac hypertrophy (P = 0.021), hypertension subgrouped for organ damage (P = 0.006), and female sex (P = 0.004), and a tendency towards a negative association with Alzheimer’s disease neuropathologic change (P = 0.048).Conclusion: The raspberry density of the frontal cortex increases with advancing age, but our results also indicate associations with acquired pathologies. Awareness of the biological and pathological context where raspberries occur can guide further research on their origin.
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| 47. |
- Ek Olofsson, Henric, et al.
(author)
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On the regional distribution of cerebral microvascular ‘raspberries’ and their association with cerebral atherosclerosis and acute circulatory failure
- 2023
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In: Cerebral Circulation - Cognition and Behavior. - : Elsevier BV. - 2666-2450. ; 4, s. 1-5
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Journal article (peer-reviewed)abstract
- IntroductionIn this follow-up study, cerebral microvascular formations termed ‘raspberries’ were quantified according to cerebral atherosclerosis (C-ASCL) and acute circulatory failure (ACF). We also examined the regional distribution of raspberries throughout the brain.Materials and methodsThe study population consisted of adult individuals who had undergone a diagnostic neuropathological autopsy. Groups were formed to examine the association between raspberries, C-ASCL and ACF (control group, C-ASCL group, C-ASCL+ACF group [n = 47 per group] and a combined C-ASCL-tot group [n = 94]). To examine the regional distribution, additional groups were formed based on previously known raspberry densities of the frontal cortex (high-, medium- and low-density group [n = 6 per group]). Raspberries were quantified on scanned haematoxylin-eosin-stained sections.ResultsCortical raspberry density did not differ at a statistically significant level between the control group, the C-ASCL group and the C-ASCL+ACF group (P = 0.10) but did so between the control group and the C-ASCL-tot group (P = 0.033). The total raspberry density of the high-, medium- and low-density groups differed at a statistically significant level (P = 0.005), which remained in group-to-group comparisons of the high- and medium-density groups (P = 0.015) and the high- and low-density groups (P = 0.002). Raspberries were rare in cerebral white matter and in the cerebellum.ConclusionAn association between raspberry density and C-ASCL is supported but is weaker than previously indicated. An association with ACF is not indicated. The raspberry density of the frontal cortex provides an approximation of the brain's total raspberry density.
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| 48. |
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| 49. |
- Ekman, Linnéa, et al.
(author)
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Evaluation of small nerve fiber dysfunction in type 2 diabetes
- 2020
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 141:1, s. 38-46
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Journal article (peer-reviewed)abstract
- Objectives: To assess potential correlations between intraepidermal nerve fiber densities (IENFD), graded with light microscopy, and clinical measures of peripheral neuropathy in elderly male subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM), respectively. Materials and methods: IENFD was assessed in thin sections of skin biopsies from distal leg in 86 men (71-77 years); 24 NGT, 15 IGT, and 47 T2DM. Biopsies were immunohistochemically stained for protein gene product (PGP) 9.5, and intraepidermal nerve fibers (IENF) were quantified manually by light microscopy. IENFD was compared between groups with different glucose tolerance and related to neurophysiological tests, including nerve conduction study (NCS; sural and peroneal nerve), quantitative sensory testing (QST), and clinical examination (Total Neuropathy Score; Neuropathy Symptom Score and Neuropathy Disability Score). Results: Absent IENF was seen in subjects with T2DM (n = 10; 21%) and IGT (n = 1; 7%) but not in NGT. IENFD correlated weakly negatively with HbA1c (r = −.268, P =.013) and Total Neuropathy Score (r = −.219, P =.042). Positive correlations were found between IENFD and sural nerve amplitude (r =.371, P =.001) as well as conduction velocity of both the sural (r =.241, P =.029) and peroneal nerve (r =.258, P =.018). Proportions of abnormal sural nerve amplitude became significantly higher with decreasing IENFD. No correlation was found with QST. Inter-rater reliability of IENFD assessment was good (ICC = 0.887). Conclusions: Signs of neuropathy are becoming more prevalent with decreasing IENFD. IENFD can be meaningfully evaluated in thin histopathological sections using the presented technique to detect neuropathy.
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| 50. |
- Ekman, Linnéa, et al.
(author)
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Temporal trend of small nerve fibre degeneration in people with and without type 2 diabetes mellitus
- 2022
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In: Diabetic Medicine. - : John Wiley & Sons. - 0742-3071 .- 1464-5491. ; 39:3
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Journal article (peer-reviewed)abstract
- Aims: We investigated the long-term temporal trend of intraepidermal nerve fibre density (IENFD) and the association between changes in IENFD and metabolic factors in individuals with and without type 2 diabetes. Methods: A total of 66 participants were enrolled in this longitudinal population-based study, at baseline consisting of 35 individuals (median 61 years) without diabetes and 31 individuals with type 2 diabetes mellitus. Participants underwent clinical and electrophysiological examinations, as well as a skin biopsy both at baseline and at the follow-up visit (mean 8.1 ± 0.5 years). IENFD was assessed in thin sections of 5 μm, stained with the protein gene product 9.5-antibody and compared between the groups. Results: IENFD decreased during the period in both groups, with a greater decline in the group without diabetes than in type 2 diabetes (−2.3 and −0.6 fibres/mm respectively; p < 0.001). While IENFD at baseline was significantly reduced in type 2 diabetes relative to people without (p < 0.001), no difference in IENFD was found between groups at the follow-up (p = 0.183). Linear mixed model analysis indicated that age, weight and HbA1c were associated with decrease in IENFD in the total population (p < 0.007). IENFD also decreased with increasing age and weight, but not with HbA1c, in the separate groups (p < 0.049). Conclusions: Despite lower IENFD levels at baseline in type 2 diabetes, IENFD was equal between the groups at follow-up. A decrease in IENFD is to a limited extent affected by body weight, and HbA1c, but age seems to be the long-term determinant of IENFD in an elderly population.
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