Publications by authors named "Pia Sundgren"

109 Publications

Cognitive interference processing in adult survivors of childhood acute lymphoblastic leukemia using functional magnetic resonance imaging.

Acta Oncol 2021 Oct 12:1-8. Epub 2021 Oct 12.

Department of Oncology, Skåne University Hospital, Lund, Sweden.

Background: Childhood acute lymphoblastic leukemia (ALL) is associated with cognitive impairment in adulthood. Cognitive interference processing and its correlated functional magnetic resonance imaging (fMRI) activity in the brain have not yet been studied in this patient group.

Material: Twenty-six adult childhood ALL survivors (median [interquartile range {IQR}] age, 40.0 [37.0-42.3] years) were investigated at median age (IQR), 35.0 (32.0-37.0) years after treatment with intrathecal and intravenous chemotherapy as well as cranial radiotherapy (24 Gy) and compared with 26 matched controls (median [IQR] age, 37.5 [33.0-41.5] years).

Methods: Cognitive interference processing was investigated in terms of behavioral performance (response times [ms] and accuracy performance [%]) and fMRI activity in the cingulo-fronto-parietal (CFP) attention network as well as other parts of the brain using the multisource interference task (MSIT).

Results: ALL survivors had longer response times and reduced accuracy performance during cognitive interference processing (median [IQR] interference effect, 371.9 [314.7-453.3] ms and 6.7 [4.2-14.7]%, respectively) comparedwith controls (303.7 [275.0-376.7] ms and 2.3 [1.6-4.3]%, respectively), but did not exhibit altered fMRI activity in the CFP attention network or elsewhere in the brain.

Conclusion: Adult childhood ALL survivors demonstrated impaired behavioral performance but no altered fMRI activity when performing cognitive interference processing when compared with controls. The results can be used to better characterize this patient group and to optimize follow-up care and support for these individuals.
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http://dx.doi.org/10.1080/0284186X.2021.1987514DOI Listing
October 2021

Towards robust glucose chemical exchange saturation transfer imaging in humans at 3 T: Arterial input function measurements and the effects of infusion time.

NMR Biomed 2021 Sep 29:e4624. Epub 2021 Sep 29.

Department of Medical Radiation Physics, Lund University, Lund, Sweden.

Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3 T (around 1%) and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements. In this study, the aim was to study DGE arterial input functions (AIFs) in healthy volunteers at 3 T for different scanning protocols, as a step towards making the glucose chemical exchange saturation transfer (glucoCEST) protocol more robust. Two different infusion durations (1.5 and 4.0 min) and saturation frequency offsets (1.2 and 2.0 ppm) were used. The effect of subject motion on the DGE signal was studied by using motion estimates retrieved from standard retrospective motion correction to create pseudo-DGE maps, where the apparent DGE signal changes were entirely caused by motion. Furthermore, the DGE AIFs were compared with venous blood glucose levels. A significant difference (p = 0.03) between arterial baseline and postinfusion DGE signal was found after D-glucose infusion. The results indicate that the measured DGE AIF signal change depends on both motion and blood glucose concentration change, emphasizing the need for sufficient motion correction in glucoCEST imaging. Finally, we conclude that a longer infusion duration (e.g. 3-4 min) should preferably be used in glucoCEST experiments, because it can minimize the glucose infusion side effects without negatively affecting the DGE signal change.
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http://dx.doi.org/10.1002/nbm.4624DOI Listing
September 2021

Cognitive interference processing in adults with childhood craniopharyngioma using functional magnetic resonance imaging.

Endocrine 2021 Jul 22. Epub 2021 Jul 22.

Department of Endocrinology, Skåne University Hospital, Lund, Sweden.

Purpose: To assess cognitive interference processing in adults with childhood craniopharyngioma (CP), with and without hypothalamic injury, respectively, in terms of behavioral performance and functional magnetic resonance imaging (fMRI) activity, using the multi-source interference task (MSIT).

Methods: Twenty-eight CP patients (median age 34.5 [29.0-39.5] years) were investigated at median 20.5 (16.3-28.8) years after treatment with surgical resection and in some cases additional radiotherapy (n = 10) and compared to 29 matched controls (median age 37.0 [32.5-42.0] years). The subjects performed the MSIT during fMRI acquisition and behavioral performance in terms of response times (ms) and accuracy performance (%) were recorded.

Results: The MSIT activated the cingulo-fronto-parietal (CFP) attention network in both CP patients and controls. No differences were found in behavioral performance nor fMRI activity between CP patients (interference effect 333.9 [287.3-367.1] ms and 3.1 [1.6-5.6]%, respectively) and controls (309.1 [276.4-361.0] ms and 2.6 [1.6-4.9]%). No differences were found in behavioral performance nor fMRI activity between the two subgroups with (332.0 [283.6-353.4] ms and 4.2 [2.3-5.7]%, respectively) and without hypothalamic injury (355.7 [293.7-388.7] ms and 2.1 [1.0-5.2]%, respectively), respectively, and controls.

Conclusion: Adults with childhood CP performed cognitive interference processing equally well as controls and demonstrated no compensatory fMRI activity in the CFP attention network compared to controls. This was also true for the two subgroups with and without hypothalamic injury. The results can be useful to better characterize this condition, and to optimize treatment and support for these individuals.
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http://dx.doi.org/10.1007/s12020-021-02824-9DOI Listing
July 2021

Structural Changes on MRI Demonstrate Specific Cerebellar Involvement in SLE Patients-A VBM Study.

Brain Sci 2021 Apr 16;11(4). Epub 2021 Apr 16.

Department of Clinical Sciences Lund, Diagnostic Radiology, Faculty of Medicine, Lund University, 221 00 Lund, Sweden.

The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with neuropsychiatric manifestations (NPSLE) than those without (non-NPSLE). Structural T1-weighted MRI was performed on 69 female SLE patients (mean age = 35.8 years, range = 18-51 years) and 24 age-matched female HC (mean age = 36.8 years, range = 23-52 years) in conjunction with neuropsychological assessment using the CNS Vital Signs test battery. T1-weighted images were preprocessed and analyzed by FSL-VBM. The results show that SLE patients had lower grey matter probability values than the control group in the VIIIa of the cerebellum bilaterally, a region that has previously been implied in sensorimotor processing in human and non-human primates. No structural differences for this region were found between NPSLE and non-NPSLE patients. VBM values from the VIIIa region showed a weak positive correlation with the psychomotor speed domain from CNS Vital Signs ( = 0.05, = 0.21), which is in line with its presumed role as a sensorimotor processing area.
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http://dx.doi.org/10.3390/brainsci11040510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072619PMC
April 2021

Assessment of Amide proton transfer weighted (APTw) MRI for pre-surgical prediction of final diagnosis in gliomas.

PLoS One 2020 29;15(12):e0244003. Epub 2020 Dec 29.

Division of Radiology, Department of Clinical Sciences, Lund University, Lund, Sweden.

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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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244003PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771875PMC
February 2021

Longitudinal study of cognitive function in glioma patients treated with modern radiotherapy techniques and standard chemotherapy.

Acta Oncol 2020 Sep 17;59(9):1091-1097. Epub 2020 Jun 17.

Department of Clinical Sciences, Division of Radiology, Lund University, Lund, Sweden.

: Cognitive function is an important outcome measure in patients with brain tumor, providing information about the patient's clinical situation, treatment effects and possible progressive disease. The aim of this longitudinal study was to evaluate effects of the currently used radiation and chemotherapy treatment on cognitive function and to investigate associations between cognitive function at baseline and progression as well as overall survival.: 32 patients newly diagnosed with malignant glioma were evaluated at baseline with CNS Vital Signs (CNS-VS), a computerized standardized neuropsychological test battery, prior to arc-based radiotherapy and concomitant chemotherapy with Temozolomide. CNS-VS measures the cognitive functions known to be affected in patients with brain tumor, covering nine cognitive domains. Follow-up cognitive evaluations were performed in 26 patients after 3.5 months and in 13 patients 1 year after treatment start.: Overall cognitive scores were lower in the studied patient cohort at baseline compared to standardized domain scores. At 3.5 months follow-up cognitive functioning was slightly decreased, but only in 1/9 cognitive domains - visual memory - where significant changes were found compared to baseline test results. Similarly, at 12 months follow-up no significant changes in cognitive test results were seen compared to baseline examination, except for a decrease in the visual memory domain. In relation to early progression, the most significant cognitive deficits were dysfunctional visual memory and low executive functioning at baseline. Low executive function at baseline correlated most significantly with shorter overall survival.: The present study suggests that the currently used arc-based radiotherapy and chemotherapy might affect cognitive function less negatively than previously described during treatment and in the first year after treatment in malignant glioma patients. In general, a high cognitive test score at baseline was associated with longer time to progression and with longer survival.
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http://dx.doi.org/10.1080/0284186X.2020.1778181DOI Listing
September 2020

Tensor-valued diffusion MRI in under 3 minutes: an initial survey of microscopic anisotropy and tissue heterogeneity in intracranial tumors.

Magn Reson Med 2020 02 13;83(2):608-620. Epub 2019 Sep 13.

Department of Clinical Sciences Lund, Radiology, Lund University, Lund, Sweden.

Purpose: To evaluate the feasibility of a 3-minutes protocol for assessment of the microscopic anisotropy and tissue heterogeneity based on tensor-valued diffusion MRI in a wide range of intracranial tumors.

Methods: B-tensor encoding was performed in 42 patients with intracranial tumors (gliomas, meningiomas, adenomas, and metastases). Microscopic anisotropy and tissue heterogeneity were evaluated by estimating the anisotropic kurtosis (MK ) and isotropic kurtosis (MK ), respectively. An extensive imaging protocol was compared with a 3-minutes protocol.

Results: The fast imaging protocol yielded parameters with characteristics in terms of bias and precision similar to the full protocol. Glioblastomas had lower microscopic anisotropy than meningiomas (MK = 0.29 ± 0.06 vs. 0.45 ± 0.08, P = 0.003). Metastases had higher tissue heterogeneity (MK = 0.57 ± 0.07) than both the glioblastomas (0.44 ± 0.06, P < 0.001) and meningiomas (0.46 ± 0.06, P = 0.03).

Conclusion: Evaluation of the microscopic anisotropy and tissue heterogeneity in intracranial tumor patients is feasible in clinically relevant times frames.
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http://dx.doi.org/10.1002/mrm.27959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900060PMC
February 2020

Diagnostic value of alternative techniques to gadolinium-based contrast agents in MR neuroimaging-a comprehensive overview.

Insights Imaging 2019 Aug 23;10(1):84. Epub 2019 Aug 23.

Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden.

Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017.This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging.Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke.In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.
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http://dx.doi.org/10.1186/s13244-019-0771-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708018PMC
August 2019

Extracellular lipid loading augments hypoxic paracrine signaling and promotes glioma angiogenesis and macrophage infiltration.

J Exp Clin Cancer Res 2019 Jun 7;38(1):241. Epub 2019 Jun 7.

Department of Clinical Sciences Lund, Section of Oncology and Pathology, Lund University, Barngatan 4, SE-221 85, Lund, Sweden.

Background: Primary brain tumors, in particular glioblastoma (GBM), remain among the most challenging cancers. Like most malignant tumors, GBM is characterized by hypoxic stress that triggers paracrine, adaptive responses, such as angiogenesis and macrophage recruitment, rescuing cancer cells from metabolic catastrophe and conventional oncological treatments. The unmet need of strategies to efficiently target tumor "stressness" represents a strong clinical motivation to better understand the underlying mechanisms of stress adaptation. Here, we have investigated how lipid loading may be involved in the paracrine crosstalk between cancer cells and the stromal compartment of the hypoxic tumor microenvironment.

Methods: Regions from patient GBM tumors with or without the lipid loaded phenotype were isolated by laser capture microdissection and subjected to comparative gene expression analysis in parallel with cultured GBM cells with or without lipid loading. The potential involvement of extracellular lipids in the paracrine crosstalk with stromal cells was studied by immunoprofiling of the secretome and functional studies in vitro as well as in various orthotopic GBM mouse models, including hyperlipidemic ApoE-/- mice. Statistical analyses of quantitative experimental methodologies were performed using unpaired Student's T test. For survival analyses of mouse experiments, log-rank test was used, whereas Kaplan-Meier was performed to analyze patient survival.

Results: We show that the lipid loaded niche of GBM patient tumors exhibits an amplified hypoxic response and that the acquisition of extracellular lipids by GBM cells can reinforce paracrine activation of stromal cells and immune cells. At the functional level, we show that lipid loading augments the secretion of e.g. VEGF and HGF, and may potentiate the cross-activation of endothelial cells and macrophages. In line with these data, in vivo studies suggest that combined local tumor lipid loading and systemic hyperlipidemia of ApoE-/- mice receiving a high fat diet induces tumor vascularization and macrophage recruitment, and was shown to significantly decrease animal survival.

Conclusions: Together, these data identify extracellular lipid loading as a potentially targetable modulator of the paracrine adaptive response in the hypoxic tumor niche and suggest the contribution of the distinct lipid loaded phenotype in shaping the glioma microenvironment.
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http://dx.doi.org/10.1186/s13046-019-1228-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556032PMC
June 2019

Comparison of Voxel-Wise and Histogram Analyses of Glioma ADC Maps for Prediction of Early Therapeutic Change.

Tomography 2019 03;5(1):7-14

Department of Radiology, University of Michigan Medical School, Ann Arbor, MI.

Noninvasive imaging methods are sought to objectively predict early response to therapy for high-grade glioma tumors. Quantitative metrics derived from diffusion-weighted imaging, such as apparent diffusion coefficient (ADC), have previously shown promise when used in combination with voxel-based analysis reflecting regional changes. The functional diffusion mapping (fDM) metric is hypothesized to be associated with volume of tumor exhibiting an increasing ADC owing to effective therapeutic action. In this work, the reference fDM-predicted survival (from previous study) for 3 weeks from treatment initiation (midtreatment) is compared to multiple histogram-based metrics using Kaplan-Meier estimator for 80 glioma patients stratified to responders and nonresponders based on the population median value for the given metric. The ADC histogram metric reflecting reduction in midtreatment volume of solid tumor (ADC < 1.25 × 10 mm/s) by >8% population-median with respect to pretreatment is found to have the same predictive power as the reference fDM of increasing midtreatment ADC volume above 4%. This study establishes the level of correlation between fDM increase and low-ADC tumor volume shrinkage for prediction of early response to radiation therapy in patients with glioma malignancies.
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http://dx.doi.org/10.18383/j.tom.2018.00049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403028PMC
March 2019

Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy - a diffusional kurtosis study.

Acta Oncol 2019 Jul 12;58(7):1021-1028. Epub 2019 Feb 12.

e Department of Endocrinology , Skåne University hospital , Lund , Sweden.

Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) are MRI techniques that quantify microstructural changes in brain white matter (WM) and DKI is regarded as the more sensitive of them. Our aim was to more thoroughly understand the nature of cognitive deficits after cranial radiotherapy (CRT) in adulthood after childhood ALL. Thirty-eight (21 women) ALL survivors, median age 38 (27-46) years, were investigated at median 34 years after diagnosis. All had been treated with a CRT dose of 24 Gy and with 11 years of complete hormone supplementation. DTI and DKI parameters were determined and neurocognitive tests were performed in ALL survivors and 29 matched controls. ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention ( < .001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all  < .05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum ( < .05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory ( = -0.40,  < .04). The left and right uncinate fasciculus ( = 0.6,  < .001), ( = -0.5,  < .02) as well as the right ventral cingulum ( = 0.5,  < .007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus ( = 0.3,  = 0.05,  = .02), and ventral cingulum ( = 0.3,  = .02) were associated with impaired results of episodic visual memory. ALL survivors with cognitive deficits demonstrated microstructural damage in several WM tracts that were more extensive with DKI as compared to DTI; this might be a marker of radiation and chemotherapy neurotoxicity underlying cognitive dysfunction.
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http://dx.doi.org/10.1080/0284186X.2019.1571279DOI Listing
July 2019

Functional connectivity changes in core resting state networks are associated with cognitive performance in systemic lupus erythematosus.

J Comp Neurol 2019 08 19;527(11):1837-1856. Epub 2019 Feb 19.

Division of Clinical Radiology, Department of Clinical Sciences, Lund University, Lund, Sweden.

To investigate core resting state networks in SLE patients with and without neuropsychiatric symptoms by examining functional connectivity changes correlating with results of cognitive testing. Structural MRI and resting state-fMRI (rs-fMRI) were performed in 61 female SLE patients (mean age: 36.8 years, range 18.2-52.0 years) and 20 healthy controls (HC) (mean age 36.2 years, range 23.3-52.2 years) in conjunction with clinical examination and cognitive testing. Alterations in core resting state networks, not found in our healthy controls sample, correlated with cognitive performance gauged by neuropsychological tests in non-neuropsychiatric SLE (nNP) as well as in neuropsychiatric SLE patients (NP). The observed pattern of increased functional connectivity in core resting state networks correlated with reduced cognitive performance on all cognitive domains tested and with a heavy focus on DM, CE, and DM-CE in the NP subgroup. Furthermore, we found that the observed alterations in memory and psychomotor speed correlated with disease duration. In SLE patients both with and without clinically overt neuropsychiatric manifestations, we found changes in the functional connectivity of core resting state networks essential to cognitive functions. These findings may represent a rewiring of functional architecture in response to neuronal damage and could indicate suboptimal compensatory mechanisms at play.
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http://dx.doi.org/10.1002/cne.24656DOI Listing
August 2019

Ultrasensitive Immunoprofiling of Plasma Extracellular Vesicles Identifies Syndecan-1 as a Potential Tool for Minimally Invasive Diagnosis of Glioma.

Clin Cancer Res 2019 05 24;25(10):3115-3127. Epub 2019 Jan 24.

Department of Clinical Sciences, Lund, Section of Oncology and Pathology, Lund University, Lund, Sweden.

Purpose: Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for noninvasive diagnosis of glioma.

Experimental Design: PlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis, and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay-based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort ( = 82).

Results: Among potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high-grade glioblastoma multiforme (GBM, WHO grade IV) and low-grade glioma [LGG, WHO grade II; area under the ROC curve (AUC): 0.81; sensitivity: 71%; specificity: 91%]. These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91; sensitivity: 79%; specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEV originating from GBM tumors, as plEV correlated with SDC1 protein expression in matched patient tumors, and plEV was decreased postoperatively depending on the extent of surgery.

Conclusions: Our studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-2946DOI Listing
May 2019

Brain myoinositol as a potential marker of amyloid-related pathology: A longitudinal study.

Neurology 2019 01 4;92(5):e395-e405. Epub 2019 Jan 4.

From the Division of Clinical Geriatrics (O.V., K.P., L.-O.W., E.W.), Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm; Department of Diagnostic Radiology (P.S., D.v.W.), Lund University; Imaging and Function (D.v.W.), Skåne University Health Care, Lund; Clinical Memory Research Unit (S.P., E.S., O.H.), Department of Clinical Sciences, Malmö, Lund University; Memory Clinic (E.S., O.H.), Skåne University Hospital, Malmö, Sweden; and Department of Neuroimaging (E.W.), Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.

Objective: To investigate the association between longitudinal changes in proton magnetic resonance spectroscopy (MRS) metabolites and amyloid pathology in individuals without dementia, and to explore the relationship between MRS and cognitive decline.

Methods: In this longitudinal multiple time point study (a subset of the Swedish BioFINDER), we included cognitively healthy participants, individuals with subjective cognitive decline, and individuals with mild cognitive impairment. MRS was acquired serially in 294 participants (670 individual spectra) from the posterior cingulate/precuneus. Using mixed-effects models, we assessed the association between MRS and baseline β-amyloid (Aβ), and between MRS and the longitudinal Mini-Mental State Examination, accounting for , age, and sex.

Results: While baseline MRS metabolites were similar in Aβ positive (Aβ+) and negative (Aβ-) individuals, in the Aβ+ group, the estimated rate of change was +1.9%/y for myo-inositol (mI)/creatine (Cr) and -2.0%/y for -acetylaspartate (NAA)/mI. In the Aβ- group, mI/Cr and NAA/mI yearly change was -0.05% and +1.2%; however, this was not significant across time points. The mild cognitive impairment Aβ+ group showed the steepest MRS changes, with an estimated rate of +2.93%/y ( = 0.07) for mI/Cr and -3.55%/y ( < 0.01) for NAA/mI. Furthermore, in the entire cohort, we found that Aβ+ individuals with low baseline NAA/mI had a significantly higher rate of cognitive decline than Aβ+ individuals with high baseline NAA/mI.

Conclusion: We demonstrate that the longitudinal change in mI/Cr and NAA/mI is associated with underlying amyloid pathology. MRS may be a useful noninvasive marker of Aβ-related processes over time. In addition, we show that in Aβ+ individuals, baseline NAA/mI may predict the rate of future cognitive decline.
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http://dx.doi.org/10.1212/WNL.0000000000006852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369900PMC
January 2019

Multivoxel H-MR Spectroscopy Biometrics for Preoprerative Differentiation Between Brain Tumors.

Tomography 2018 Dec;4(4):172-181

Departments of Clinical Sciences/Division of Radiology.

We investigated multivoxel proton magnetic resonance spectroscopy (H-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. H-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 ( < .001) and LGG/MET ( < .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 ( < .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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http://dx.doi.org/10.18383/j.tom.2018.00051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299741PMC
December 2018

Arterial Input Functions and Tissue Response Curves in Dynamic Glucose-Enhanced (DGE) Imaging: Comparison Between glucoCEST and Blood Glucose Sampling in Humans.

Tomography 2018 Dec;4(4):164-171

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD.

Dynamic glucose-enhanced (DGE) imaging uses chemical exchange saturation transfer magnetic resonance imaging to retrieve information about the microcirculation using infusion of a natural sugar (D-glucose). However, this new approach is not yet well understood with respect to the dynamic tissue response. DGE time curves for arteries, normal brain tissue, and cerebrospinal fluid (CSF) were analyzed in healthy volunteers and compared with the time dependence of sampled venous plasma blood glucose levels. The arterial response curves (arterial input function [AIF]) compared reasonably well in shape with the time curves of the sampled glucose levels but could also differ substantially. The brain tissue response curves showed mainly negative responses with a peak intensity that was of the order of 10 times smaller than the AIF peak and a shape that was susceptible to both noise and partial volume effects with CSF, attributed to the low contrast-to-noise ratio. The CSF response curves showed a rather large and steady increase of the glucose uptake during the scan, due to the rapid uptake of D-glucose in CSF. Importantly, and contrary to gadolinium studies, the curves differed substantially among volunteers, which was interpreted to be caused by variations in insulin response. In conclusion, while AIFs and tissue response curves can be measured in DGE experiments, partial volume effects, low concentration of D-glucose in tissue, and osmolality effects between tissue and blood may prohibit quantification of normal tissue perfusion parameters. However, separation of tumor responses from normal tissue responses would most likely be feasible.
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http://dx.doi.org/10.18383/j.tom.2018.00025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299743PMC
December 2018

Active NET formation in Libman-Sacks endocarditis without antiphospholipid antibodies: A dramatic onset of systemic lupus erythematosus.

Autoimmunity 2018 09 28;51(6):310-318. Epub 2018 Oct 28.

b Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine , Linköping University , Linköping , Sweden.

Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman-Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman-Sacks endocarditis, could not be detected. Instead, we observed active NET formation in the tissue of the mitral valve, as well as in the circulation. Levels of NET remnants were significantly higher in serially obtained sera from the patient compared with sex-matched blood donors (p = .0011), and showed a non-significant but substantial correlation with blood neutrophil counts (r = 0.65, p = .16). The specific neutrophil elastase activity measured in serum seemed to be modulated by the provided immunosuppressive treatment. In addition, we found anti-Ro60/SSA antibodies in the cerebrospinal fluid of the patient but not NET remnants or increased elastase activity. This case illustrates that different disease mechanisms mediated via autoantibodies can occur simultaneously in SLE. NET formation with release of cytotoxic NET remnants is a candidate player in the pathogenesis of this non-canonical form of Libman-Sacks endocarditis occurring in the absence of traditional antiphospholipid autoantibodies. The case description includes longitudinal results with clinical follow-up data and a discussion of the potential roles of NETs in SLE.
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http://dx.doi.org/10.1080/08916934.2018.1514496DOI Listing
September 2018

Traumatic shaking: The role of the triad in medical investigations of suspected traumatic shaking.

Acta Paediatr 2018 09;107 Suppl 472:3-23

Medical Technology, Royal Institute of Technology, Stockholm, Sweden.

The Swedish Agency for Health Technology Assessment and Assesment of Social Services (SBU) is an independent national authority, tasked by the government with assessing methods used in health, medical and dental services and social service interventions from a broad perspective, covering medical, economic, ethical and social aspects. The language in SBU's reports are adjusted to a wide audience. SBU's Board of Directors has approved the conclusions in this report. The systematic review showed the following graded results: There is limited scientific evidence that the triad (Three components of a whole. The triad associated with SBS usually comprises subdural haematoma, retinal haemorrhages and encephalopathy.) and therefore, its components can be associated with traumatic shaking (low-quality evidence). There is insufficient scientific evidence on which to assess the diagnostic accuracy of the triad in identifying traumatic shaking (very low-quality evidence). Limited scientific evidence (low-quality evidence) represents a combined assessment of studies of high or moderate quality which disclose factors that markedly weaken the evidence. It is important to note that limited scientific evidence for the reliability of a method or an effect does not imply complete lack of scientific support. Insufficient scientific evidence (very low-quality evidence) represents either a lack of studies or situations when available studies are of low quality or show contradictory results. Evaluation of the evidence was not based on formal grading of the evidence according to GRADE but on an evaluation of the total scientific basis.
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http://dx.doi.org/10.1111/apa.14473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585638PMC
September 2018

Evaluation of reproducibility in MRI quantitative volumetric assessment and its role in the prediction of overall survival and progression-free survival in glioblastoma.

Acta Radiol 2019 Apr 2;60(4):516-525. Epub 2018 Jul 2.

1 Department of Clinical Sciences, Division of Neurosurgery, Lund University and Region Skåne, Lund, Sweden.

Background: Residual tumor volume (RTV) and extent of resection (EOR) have previously been shown to affect survival in glioblastoma (GB) patients. Quantitative radiological assessment (QRA) of these factors could potentially affect clinical decision-making in the postoperative period.

Purpose: The first aim was to evaluate the reproducibility of different volume estimation methods of RTV and EOR by comparing QRA with subjective visual estimation and with objective volume estimations. The second aim was to clarify whether QRA of RTV and EOR would provide accuracy in predicting progression-free survival (PFS) and overall survival (OS) in GB patients.

Material And Methods: Seventy GB patients were studied retrospectively. Reproducibility of QRA was compared to conventional visual analysis. Intra-rater agreement between two repeated measurements of 25 patients was calculated. QRA for RTV and EOR was made for the entire study population. Survival analysis was performed by multivariate cox-regression analysis.

Results: QRA of RTV and EOR gave superior intra-rater agreement compared to subjective evaluation. Multivariate survival analysis showed prognostic significance on 18 months PFS (hazard ratio [HR] = 0.44, P = 0.003) and OS (HR = 0.42, P = 0.012) at RTV < 1.6 mL and with EOR > 96% on PFS (HR = 2.152, P = 0.005) but not on OS (HR = 1.92, P = 0.053).

Conclusion: QRA of tumor volumes is more robust compared to standard evaluation methods. Since EOR and RTV are correlated to the prognosis in GB, quantitative analysis of tumor volumes could aid decision-making and patient management postoperatively.
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http://dx.doi.org/10.1177/0284185118786060DOI Listing
April 2019

Spectroscopic differences in posterior insula in patients with chronic temporomandibular pain.

Scand J Pain 2018 07;18(3):351-361

Orofacial Pain and Jaw Function, Faculty of Odontology, Malmö University, Malmö, Sweden.

Background and aims Chronic pain including temporomandibular disorder (TMD) pain involves a complex interplay between peripheral and central sensitization, endogenous modulatory pathways, cortical processing and integration and numerous psychological, behavioral and social factors. The aim of this study was to compare spectroscopic patterns of N-Acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (MI), glutamate (Glu), and the combination of Glu and glutamine in the posterior insula in patients with chronic generalized or regional chronic TMD pain (gTMD and rTMD, respectively) compared to healthy individuals (HI) in relation to clinical findings of TMD pain. Methods Thirty-six female patients with chronic rTMD or gTMD with at least 3 months duration were included in the study. Ten healthy women were included as controls. All participants completed a questionnaire that comprised assessment of degrees of depression, anxiety, stress, catastrophizing, pain intensity, disability and locations. A clinical Diagnostic Criteria for Temporomandibular Disorders examination that comprised assessment of pain locations, headache, mouth opening capacity, pain on mandibular movement, pain on palpation and temporomandibular joint noises was performed. Pressure-pain threshold (PPT) over the masseter muscle and temporal summation to pressure stimuli were assessed with an algometer. Within a week all participants underwent non-contrast enhanced MRI on a 3T MR scanner assessing T1-w and T2-w fluid attenuation inversion recovery. A single-voxel 1H-MRS examination using point-resolved spectroscopy was performed. The metabolite concentrations of NAA, tCr, Cho, MI, Glu and Glx were analyzed with the LC model. Metabolite levels were calculated as absolute concentrations, normalized to the water signal. Metabolite concentrations were used for statistical analysis from the LC model if the Cramér-Rao bounds were less than 20%. In addition, the ratios NAA/tCr, Cho/tCr, Glu/tCr and MI/tCr were calculated. Results The results showed significantly higher tCr levels within the posterior insula in patients with rTMD or gTMD pain than in HI (p=0.029). Cho was negatively correlated to maximum mouth opening capacity with or without pain (rs=-0.42, n=28, p=0.031 and rs=-0.48, n=28, p=0.034, respectively) as well as pressure-pain threshold on the hand (rs=-0.41, n=28, p=0.031). Glu was positively correlated to temporal summation to painful mechanical stimuli (rs=0.42, n=26, p=0.034). Conclusions The present study found that increased concentrations of Cho and Glu in the posterior insular cortex is related to clinical characteristics of chronic TMD pain, including generalized pain. These findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. Implications The findings in this study have indirect implications for the diagnosis and management of TMD patients. That said, the findings provide new evidence about the critical involvement of the posterior insular cortex and the neurobiology underlying TMD pain in both regional and generalized manifestations. It is also a further step towards understanding and accepting chronic pain as a disorder in itself.
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http://dx.doi.org/10.1515/sjpain-2017-0159DOI Listing
July 2018

Imaging brain tumour microstructure.

Neuroimage 2018 11 8;182:232-250. Epub 2018 May 8.

Lund University, Department of Clinical Sciences Lund, Radiology, Lund, Sweden.

Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called 'microstructure imaging'. The promise of microstructure imaging is one of 'virtual biopsy' with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging.
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http://dx.doi.org/10.1016/j.neuroimage.2018.04.075DOI Listing
November 2018

Easier to see the speck in your critical peers' eyes than the log in your own? Response to Debelle .

Arch Dis Child 2018 07 4;103(7):714. Epub 2018 May 4.

Department of Community Medicine and Rehabilitation, Forensic Medicine, Umeå, Sweden.

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http://dx.doi.org/10.1136/archdischild-2018-315380DOI Listing
July 2018

Brain Tumor Characterization Using Multibiometric Evaluation of MRI.

Tomography 2018 Mar;4(1):14-25

Department of Radiology, Clinical Sciences Lund, Lund University, Lund, Sweden.

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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http://dx.doi.org/10.18383/j.tom.2017.00020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5903291PMC
March 2018

Functional Connectivity Changes in Systemic Lupus Erythematosus: A Resting-State Study.

Brain Connect 2018 05 5;8(4):220-234. Epub 2018 Apr 5.

7 Department of Clinical Sciences , Lund/Memory Research Unit, Lund University, Lund, Sweden .

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.
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http://dx.doi.org/10.1089/brain.2017.0557DOI Listing
May 2018

Altered white matter microstructure in lupus patients: a diffusion tensor imaging study.

Arthritis Res Ther 2018 02 7;20(1):21. Epub 2018 Feb 7.

Department of Clinical Sciences Lund/Diagnostic Radiology, Lund University, Lund, Sweden.

Background: The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms.

Methods: Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2-52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3-51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE).

Results: Comparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p = 0.038), the mid-sagittal corpus callosum (CC) (p = 0.050), and the forceps minor of the CC (p = 0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p = 0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p < 0.05). No correlations were found between DTI parameters and white matter hyperintensities, SLE Disease Activity Index-2000, Systemic Lupus International Collaborating Clinical/ACR Organ Damage Index, or Montgomery Asberg Depression Rate Score Self-report.

Conclusions: We found alterations of white matter microstructure in SLE patients that were related to disease duration and fatigue. Our results indicate that cerebral involvement in SLE is not isolated to the NPSLE subgroup.
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http://dx.doi.org/10.1186/s13075-018-1516-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803933PMC
February 2018

Pouring out the dirty bathwater without throwing away either the baby or its parents: commentary to Saunders et al.

Pediatr Radiol 2018 02 23;48(2):284-286. Epub 2017 Oct 23.

Department of Community Medicine and Rehabilitation, Forensic Medicine, Umeå University, Umeå, Sweden.

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http://dx.doi.org/10.1007/s00247-017-4003-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790846PMC
February 2018

The effect of white matter hyperintensities on statistical analysis of diffusion tensor imaging in cognitively healthy elderly and prodromal Alzheimer's disease.

PLoS One 2017 21;12(9):e0185239. Epub 2017 Sep 21.

Diagnostic Radiology, Lund University, Lund, Sweden.

Diffusion tensor imaging (DTI) has been used to study microstructural white matter alterations in a variety of conditions including normal aging and Alzheimer's disease (AD). White matter hyperintensities (WMH) are common in cognitively healthy elderly as well as in AD and exhibit elevated mean diffusivity (MD) and reduced fractional anisotropy (FA). However, the effect of WMH on statistical analysis of DTI estimates has not been thoroughly studied. In the present study we address this in two ways. First, we investigate the effect of WMH on MD and FA in the dorsal and ventral cingulum, the superior longitudinal fasciculus, and the corticospinal tract, by comparing two matched groups of cognitively healthy elderly (n = 21 + 21) with unequal WMH load. Second, we assess the effects of adjusting for WMH load when comparing MD and FA in prodromal AD subjects (n = 83) to cognitively healthy elderly (n = 132) in the abovementioned white matter tracts. Results showed the WMH in cognitively healthy elderly to have a generally large effect on DTI estimates (Cohen's d = 0.63 to 1.27 for significant differences in MD and -1.06 to -0.69 for FA). These effect sizes were comparable to those of various neurological and psychiatric diseases (Cohen's d = 0.57 to 2.20 for differences in MD and -1.76 to -0.61 for FA). Adjusting for WMH when comparing DTI estimates in prodromal AD subjects to cognitively healthy elderly improved the explanatory power as well as the outcome of the analysis, indicating that some of the differences in MD and FA were largely driven by unequal WMH load between the groups rather than alterations in normal-appearing white matter (NAWM). Thus, our findings suggest that if the purpose of a study is to compare alterations in NAWM between two groups using DTI it may be necessary to adjust the statistical analysis for WMH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185239PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608410PMC
October 2017
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