| 1. |
- Fahlström, Markus, et al.
(författare)
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Dynamic contrast-enhanced magnetic resonance imaging may act as a biomarker for vascular damage in normal appearing brain tissue after radiotherapy in patients with glioblastoma
- 2018
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Ingår i: Acta Radiologica Open. - : Sage Publications. - 2058-4601. ; 7:11
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising perfusion method and may be useful in evaluating radiation-induced changes in normal-appearing brain tissue.PurposeTo assess whether radiotherapy induces changes in vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) derived from DCE-MRI in normal-appearing brain tissue and possible relationships to radiation dose given.Material and MethodsSeventeen patients with glioblastoma treated with radiotherapy and chemotherapy were included; five were excluded because of inconsistencies in the radiotherapy protocol or early drop-out. DCE-MRI, contrast-enhanced three-dimensional (3D) T1-weighted (T1W) images and T2-weighted fluid attenuated inversion recovery (T2-FLAIR) images were acquired before and on average 3.3, 30.6, 101.6, and 185.7 days after radiotherapy. Pre-radiotherapy CE T1W and T2-FLAIR images were segmented into white and gray matter, excluding all non-healthy tissue. Ktrans and Ve were calculated using the extended Kety model with the Parker population-based arterial input function. Six radiation dose regions were created for each tissue type, based on each patient’s computed tomography-based dose plan. Mean Ktrans and Ve were calculated over each dose region and tissue type.ResultsGlobal Ktrans and Ve demonstrated mostly non-significant changes with mean values higher for post-radiotherapy examinations in both gray and white matter compared to pre-radiotherapy. No relationship to radiation dose was found.ConclusionAdditional studies are needed to validate if Ktrans and Ve derived from DCE-MRI may act as potential biomarkers for acute and early-delayed radiation-induced vascular damages. No dose-response relationship was found.
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| 2. |
- Fahlström, Markus, et al.
(författare)
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Perfusion magnetic resonance imaging changes in normal appearing brain tissue after radiotherapy in glioblastoma patients may confound longitudinal evaluation of treatment response
- 2018
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Ingår i: Radiology and Oncology. - : Walter de Gruyter. - 1318-2099 .- 1581-3207. ; 52:2, s. 143-151
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was assess acute and early delayed radiation-induced changes in normal-appearing brain tissue perfusion as measured with perfusion magnetic resonance imaging (MRI) and the dependence of these changes on the fractionated radiotherapy (FRT) dose level.Patients and methods: Seventeen patients with glioma WHO grade III-IV treated with FRT were included in this prospective study, seven were excluded because of inconsistent FRT protocol or missing examinations. Dynamic susceptibility contrast MRI and contrast-enhanced 3D-T1-weighted (3D-T1w) images were acquired prior to and in average (standard deviation): 3.1 (3.3), 34.4 (9.5) and 103.3 (12.9) days after FRT. Pre-FRT 3D-T1w images were segmented into white-and grey matter. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were calculated and co-registered patient-wise to pre-FRT 3D-T1w images. Seven radiation dose regions were created for each tissue type: 0-5 Gy, 5-10 Gy, 10-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy and 50-60 Gy. Mean CBV and CBF were calculated in each dose region and normalised (nCBV and nCBF) to the mean CBV and CBF in 0-5 Gy white-and grey matter reference regions, respectively.Results: Regional and global nCBV and nCBF in white-and grey matter decreased after FRT, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in grey matter.Conclusions: Our data suggest that radiation-induced perfusion changes occur in normal-appearing brain tissue after FRT. This can cause an overestimation of relative tumour perfusion using dynamic susceptibility contrast MRI, and can thus confound tumour treatment evaluation.
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| 3. |
- Kockum, Karin, et al.
(författare)
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Diagnostic accuracy of the iNPH Radscale in idiopathic normal pressure hydrocephalus
- 2020
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The idiopathic normal pressure hydrocephalus (iNPH) Radscale was developed to standardize the evaluation of radiological signs in iNPH. The purpose of this study was to estimate the diagnostic accuracy of the iNPH Radscale in a sample of "true positive" and "true negative" cases.Methods: Seventy-five patients with definite iNPH, i.e. who had improved at clinical follow-up one year after ventriculoperitoneal shunt surgery, were compared with 55 asymptomatic individuals from the general population. A radiologist assessed the seven radiological features of the iNPH Radscale in computed tomography of the brain in the patients (preoperatively) and controls.Results: The iNPH Radscale score was significantly higher in the iNPH group (Median = 10, interquartile range 9–11) than in the control group (Median = 1, interquartile range 1–2) (p <0.001). Receiver operated characteristics analysis yielded an area under the curve of 99.7%, and an iNPH Radscale score ≤ 4 identified those without iNPH, with a sensitivity of 100%, specificity of 96% and overall accuracy of 98.5%.Conclusions: In this study, iNPH Radscale could accurately discriminate between patients with definite iNPH and asymptomatic individuals over 65 years old. According to the results, a diagnosis of iNPH is very likely in patients with an iNPH Radscale score above 8 and corresponding clinical symptoms. On the other hand, the diagnosis should be questioned when the iNPH Radscale score is below the cut-off level of 4. We conclude that the iNPH Radscale could work as a diagnostic screening tool to detect iNPH. Whether the scale also can be used to predict shunt outcome needs further studies.
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| 4. |
- Kockum, Karin, 1981-
(författare)
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Imaging in Idiopathic Normal Pressure Hydrocephalus : The value of structured radiological evaluation
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Idiopathic normal pressure hydrocephalus (iNPH) is a neurological condition where the symptoms include disturbed gait, balance, cognition and continence. The diagnostic guidelines are based on typical symptoms combined with imaging showing enlarged ventricles. Several scales for evaluating symptoms exist, but no corresponding tool is in use for imaging. The aim of this thesis was to construct a radiological scoring system, the iNPH Radscale, to facilitate radiological evaluation and systematic reporting of changes. Further, to test the reliability and accuracy of the scale and evaluate the usefulness for longitudinal monitoring.Methods: In paper I 168 individuals over 65 years of age from the general population underwent computed tomography (CT) of the brain and a neurological examination, and the same cohort was followed up 2 years later in paper IV. The iNPH Radscale was developed in these papers and further validated in papers II and III. Papers II and III included surgically treated iNPH patients with preoperative imaging of the brain. Thirty-five patients were included in paper II comparing preoperative CT and magnetic resonance imaging (MRI) using the iNPH Radscale. Paper III included 75 shunt responsive patients and 55 asymptomatic controls to evaluate the accuracy of the iNPH Radscale.Results: In paper I, seven parameters summarized as a total iNPH Radscale score were significantly associated with clinical iNPH symptoms (r = 0.55, p < 0.001). In paper II, the agreement between CT and MRI was substantial to almost perfect (kappa and intraclass correlation, 0.60–0.91, p < 0.001) for all parameters except periventricular white matter changes. In paper III the iNPH Radscale score was significantly higher in the iNPH group than the control group (p <0.001). Receiver operating characteristics analysis yielded an area under the curve of 99.7 %, and an iNPH Radscale score £ 4 identified those without iNPH (sensitivity 100 %, specificity 96 % and overall accuracy 98.5 %). In paper IV, symptomatic participants had significantly higher iNPH Radscale scores at baseline and follow-up.Conclusions: The iNPH Radscale summarizes seven imaging features from the diagnostic guidelines and is applicable to both CT and MRI. INPH is very likely in patients with an iNPH Radscale score ³ 8 and corresponding clinical symptoms. On the other hand, the diagnosis should be questioned when the iNPH Radscale score is less than the cut-off of 4. In summary, the iNPH Radscale may become a relevant diagnostic tool for standardized evaluation in the workup of patients with suspected iNPH, as a diagnostic checklist and as a screening tool for detection with the potential for ruling out the disease.
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| 5. |
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| 6. |
- Kockum, Karin, et al.
(författare)
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Standardized image evaluation in patients with idiopathic normal pressure hydrocephalus : consistency and reproducibility
- 2019
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Ingår i: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 61:12, s. 1397-1406
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Assess the agreement for two investigators between computed tomography (CT) and magnetic resonance imaging (MRI) for seven imaging features included in the iNPH Radscale, a radiological screening tool.Methods: The study included 35 patients with idiopathic normal pressure hydrocephalus (iNPH) who were treated surgically from 2011 to 2015 at Uppsala University Hospital with preoperative CT and MRI performed with maximum 3 months between scans. Seven features were assessed: Evans’ index, temporal horn size, callosal angle, periventricular white matter changes, narrow high convexity sulci, focally enlarged sulci, and enlarged Sylvian fissures. All scans were assessed by two investigators who were blinded to each other’s results and to clinical data.Results: The agreement between CT and MRI was almost perfect for Evans’ index, temporal horns, narrow sulci, and Sylvian fissures (kappa and intraclass correlation, 0.84–0.91, p ≤ 0.001). There was substantial to almost perfect agreement for callosal angle and focally enlarged sulci. The concordance between modalities was fair for changes in periventricular white matter.Conclusion: CT and MRI are equally good for assessing radiological signs associated with iNPH except for periventricular white matter changes, as MRI has superior soft tissue contrast. The other imaging features can be evaluated consistently, and assessments are reproducible independent of modality. Therefore, the iNPH Radscale is applicable to both CT and MRI and may become an important tool for standardized evaluation in the workup in patients with suspected iNPH.
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| 7. |
- Kockum, Karin, et al.
(författare)
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The idiopathic normal-pressure hydrocephalus Radscale : a radiological scale for structured evaluation
- 2018
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 25:3, s. 569-576
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Despite the important role of imaging in diagnosing idiopathic normal pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms.METHODS: In this prospective, population based study of iNPH, 168 individuals (93 females, 75 males), mean age 75 years (range 66-92 years), underwent a computed tomography (CT) of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters i.e. Evans' index, callosal angle, size of temporal horns, narrow high convexity sulci, dilated Sylvian fissures, focally dilated sulci, periventricular hypodensities and bulging of the lateral ventricular roof.RESULTS: In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, P < 0.001) between the total score of the iNPH Radscale and clinical symptoms. The interrater agreement for the included radiological parameters was high (ICC = 0.74-0.97).CONCLUSION: The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms, should raise suspicion of iNPH motivating further evaluation for shunt-surgery.
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| 8. |
- Smits, Anja, et al.
(författare)
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Neurological impairment linked with cortico-subcortical infiltration of diffuse low-grade gliomas at initial diagnosis supports early brain plasticity
- 2015
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse low-grade gliomas (DLGG) are slow-growing brain tumors that in spite of an indolent behavior at onset show a continuous expansion over time and inevitably transform into malignant gliomas. Extensive tumor resections may be performed with preservation of neurological function due to neuroplasticity that is induced by the slow tumor growth. However, DLGG prefer to migrate along subcortical pathways, and white matter plasticity is considerably more limited than gray matter plasticity. Whether signs of functional decompensating white matter that may be found as early as at disease presentation has not been systematically studied. Here, we examined 52 patients who presented with a DLGG at the time of radiological diagnosis. We found a significant correlation between neurological impairment and eloquent cortico-subcortical tumor localization, but not between neurological function and tumor volume. These results suggest that even small tumors invading white matter pathways may lack compensatory mechanisms for functional reorganization already at disease presentation.
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| 9. |
- Virhammar, Johan, et al.
(författare)
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Arterial Spin-Labeling Perfusion MR Imaging Demonstrates Regional CBF Decrease in Idiopathic Normal Pressure Hydrocephalus
- 2017
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Ingår i: American Journal of Neuroradiology. - : AMER SOC NEURORADIOLOGY. - 0195-6108 .- 1936-959X. ; 38:11, s. 2081-2088
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Regional cerebral blood flow has previously been studied in patients with idiopathic normal pressure hydrocephalus with imaging methods that require an intravenous contrast agent or expose the patient to ionizing radiation. The purpose of this study was to assess regional CBF in patients with idiopathic normal pressure hydrocephalus compared with healthy controls using the noninvasive quantitative arterial spin-labeling MR imaging technique. A secondary aim was to compare the correlation between symptom severity and CBF.MATERIALS AND METHODS: Differences in regional cerebral perfusion between patients with idiopathic normal pressure hydrocephalus and healthy controls were investigated with pseudocontinuous arterial spin-labeling perfusion MR imaging. Twenty-one consecutive patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched randomly selected healthy controls from the population registry were prospectively included. The controls did not differ from patients with respect to selected vascular risk factors. Twelve different anatomic ROIs were manually drawn on coregistered FLAIR images. The Holm-Bonferroni correction was applied to statistical analyses.RESULTS: In patients with idiopathic normal pressure hydrocephalus, perfusion was reduced in the periventricular white matter (P < .001), lentiform nucleus (P < .001), and thalamus (P < .001) compared with controls. Cognitive function in patients correlated with CBF in the periventricular white matter (r = 0.60, P < .01), cerebellum (r = 0.63, P < .01), and pons (r = 0.71, P < .001).CONCLUSIONS: Using pseudocontinuous arterial spin-labeling, we could confirm findings of a reduced perfusion in the periventricular white matter, basal ganglia, and thalamus in patients with idiopathic normal pressure hydrocephalus previously observed with other imaging techniques.
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| 10. |
- Virhammar, Johan, et al.
(författare)
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Idiopathic normal pressure hydrocephalus : cerebral perfusion measured with pCASL before and repeatedly after CSF removal
- 2014
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 34:11, s. 1771-1778
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Tidskriftsartikel (refereegranskat)abstract
- Pseudo-continuous arterial, spin labeling (pCASL) measurements were performed in 20 patients with idiopathic normal pressure hydrocephalus (iNPH) to investigate whether cerebral blood flow (CBF) increases during the first 24 hours after a cerebrospinal fluid tap test (CSF TT). Five pCASL magnetic resonance imaging (MRI) scans were performed. Two scans were performed before removal of 40 mL CSF, and the other three at 30 minutes, 4 hours, and 24 hours, respectively after the CSF TT. Thirteen different regions of interest (ROIs) were manually drawn on coregistered MR images. In patients with increased CBF in lateral and frontal white matter after the CSF TT, gait function improved more than it did in patients with decreased CBF in these regions. However, in the whole sample, there was no significant increase in CBF after CSF removal compared with baseline investigations. The repeatability of CBF measurements at baseline was high, with intraclass correlation coefficients of 0.60 to 0.90 for different ROIs, but the median regional variability was in the range of 5% to 17%. Our results indicate that CBF in white matter close to the lateral ventricles plays a role in the reversibility of symptoms after CSF removal in patients with iNPH.
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