| 1. |
- Askaner, Krister, et al.
(author)
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Differentiation of Brain Metastases due to Primary Malignancy and Glioblastomas using Dynamic Susceptibility Contrast-Enhanced MR at 3T
- 2017
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Conference paper (peer-reviewed)abstract
- Purpose:To find out differences in cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSCE-MRI) in glioblastomas and cerebral metastases. The main purpose was to compare CBV maps between metastases with different primary malignancies. Furthermore the metastasis group was compared with the glioblastoma group.Method:Conventional imaging and DSCE-MRI using 3T MRI system was performed in 114 patients, 38 glioblastomas and 76 metastases, 32 lung, 12 breast, 12 melanoma, 10 gastrointestinal (GI), and 10 other. CBV values were measured in the solid tumor area, peritumoral edema, area adjacent to peritumoral edema, and in normal apparent white matter in contralateral semioval center. The four subgroups of metastases were compared with one-way ANOVA to determine differences in CBV of significance. CBV values in glioblastomas and metastases were then statistically compared using paired t-test. Receiver -operating characteristic analysis was used to determine optimal cut-off values when parameters showed statistical differences.Results:There were no significantly differences in CBV between the four subgroups of metastases. CBV in the peritumoral edema significantly differentiated metastases from glioblastomas, p=0.0001. CBV cutoff value of 2.3 yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 87, 87, 71, and 91% respectively. Conclusions:Differentiation of glioblastomas and metastases is possible using DSCE-MRI. No statistically significant differences regarding CBV between metastases from lung, breast, melanoma, and GI were detected.
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| 2. |
- Blomstergren, Adam, et al.
(author)
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Evaluation of reproducibility in MRI quantitative volumetric assessment and its role in the prediction of overall survival and progression-free survival in glioblastoma
- 2019
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In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 60:4, s. 516-525
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Journal article (peer-reviewed)abstract
- 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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| 3. |
- 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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| 4. |
- 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
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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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| 5. |
- Falk Delgado, Anna, et al.
(author)
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Diffusion kurtosis imaging of gliomas grades II and III : a study of perilesional tumor infiltration, tumor grades and subtypes at clinical presentation
- 2017
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In: Radiology and Oncology. - : Walter de Gruyter GmbH. - 1318-2099 .- 1581-3207. ; 51:2, s. 121-129
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Journal article (peer-reviewed)abstract
- Background. Diffusion kurtosis imaging (DKI) allows for assessment of diffusion influenced by microcellular structures. We analyzed DKI in suspected low-grade gliomas prior to histopathological diagnosis. The aim was to investigate if diffusion parameters in the perilesional normal-appearing white matter (NAWM) differed from contralesional white matter, and to investigate differences between glioma malignancy grades II and III and glioma subtypes (astrocytomas and oligodendrogliomas).Patients and methods. Forty-eight patients with suspected low-grade glioma were prospectively recruited to this institutional review board-approved study and investigated with preoperative DKI at 3T after written informed consent. Patients with histologically proven glioma grades II or III were further analyzed (n=35). Regions of interest (ROIs) were delineated on T2FLAIR images and co-registered to diffusion MRI parameter maps. Mean DKI data were compared between perilesional and contralesional NAWM (student's t-test for dependent samples, Wilcoxon matched pairs test). Histogram DKI data were compared between glioma types and glioma grades (multiple comparisons of mean ranks for all groups). The discriminating potential for DKI in assessing glioma type and grade was assessed with receiver operating characteristics (ROC) curves.Results. There were significant differences in all mean DKI variables between perilesional and contralesional NAWM (p=< 0.000), except for axial kurtosis (p=0.099). Forty-four histogram variables differed significantly between glioma grades II (n=23) and III (n=12) (p=0.003-0.048) and 10 variables differed significantly between ACs (n=18) and ODs (n=17) (p=0.011-0.050). ROC curves of the best discriminating variables had an area under the curve (AUC) of 0.657-0.815.Conclusions. Mean DKI variables in perilesional NAWM differ significantly from contralesional NAWM, suggesting altered microstructure by tumor infiltration not depicted on morphological MRI. Histogram analysis of DKI data identifies differences between glioma grades and subtypes.
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| 6. |
- Falk Delgado, Anna, et al.
(author)
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Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III : A Prospective Cohort Study
- 2016
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In: Radiology research and practice. - : Hindawi Limited. - 2090-1941 .- 2090-195X. ; 2016:1, s. 1-15
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Journal article (peer-reviewed)abstract
- Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.
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| 7. |
- Follin, Cecilia, et al.
(author)
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Associations between Metabolic Risk Factors and the Hypothalamic Volume in Childhood Leukemia Survivors Treated with Cranial Radiotherapy.
- 2016
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1
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Journal article (peer-reviewed)abstract
- Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p-insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s-ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors.
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| 8. |
- Follin, Cecilia, et al.
(author)
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Hypothalamic dysfunction revealed by magnetic resonance diffusion tensor imaging in childhood leukemia survivors treated with cranial radiotherapy but not in craniopharyngeoma survivors
- 2016
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Conference paper (peer-reviewed)abstract
- Background: Metabolic complications with obesity are frequent in childhood acute lymphoblastic leukemia (ALL) survivors treated with cranial radiotherapy (CRT). Childhood onset Craniopharyngioma (CP) survivors without hypothalamic (HT) involvement are spared gross obesity. Magnetic resonance diffusion tensor imaging (DTI) provides information of microstructure function of the brain and quantified as fractional anisotrophy (FA), mean diffusivity (MD), axial and radial diffusivity (AD, RD). Since MD in HT is reportedly impaired (increased) in obese compared to non-obese subjects, we investigated DTI in the HT.Methods: Twenty nine ALL survivors on hormone supplementation were investigated 34 years after CRT (24 Gy). 17 CO-CP survivors with hormone supplementation but without HT damage were investigated. Comparisons were made with these two patient populations to 27 matched controls regarding DTI parameters in the HT and for BMI, fat mass, fat free mass and waist/hip measurements.Results: We recorded reduced FA (0.27 vs 0.29, P=0.04), and increased MD (1.13 vs 1.00, P<0.001), AD (1.41 vs 1.25, P<0.001), and RD (0.99 vs 0.86, P<0.001) in the right HT and increased MD (1.42 vs 1.25, P<0.001), AD (1.75 vs 1.58, P<0.001), and RD (1.25 vs 1.04, P<0.001) in left HT in ALL survivors compared to matched controls. The CPs showed no difference in the HT for these parameters compared to controls. ALL survivors with a BMI ≥ 25 showed elevated MD (P=0.03) and AD (P=0.02) compared to ALL survivors with a BMI < 25 and compared to controls with BMI ≥ 25 in the right HT. This was not the case in CP survivors or in controls.Conclusions: Thirty four years after CRT for ALL, DTI measures are deranged in the HT. ALL survivors with a BMI ≥ 25 were presented with worse HT dysfunction. CP survivors were unaffected. The present data suggests changes in the microstructure of the HT in these ALL survivors.
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| 9. |
- Follin, Cecilia, et al.
(author)
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Impaired brain metabolism and neurocognitive function in childhood leukemia survivors despite complete hormone supplementation in adulthood
- 2016
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 73, s. 157-165
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Journal article (peer-reviewed)abstract
- Cranial radiotherapy is a known risk factor for neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the nature of cognitive dysfunction during adulthood in ALL survivors is important as it has an impact on major life situations. Thirty-eight (21 women) ALL survivors were investigated 34 years after diagnosis. Median-age was 38 (27–46) years. All were treated with a CRT dose of 24 Gy and 11 years (3–13) of complete hormone supplementation. Comparisons were made to 29 matched controls. Assessments of magnetic resonance spectroscopy (white and grey matter metabolic alterations), brain volume and neuropsychological tests were performed. ALL survivors demonstrate a generally lower performance in neuropsychological tests. ALL survivors scored lower than controls in vocabulary (p < 0.001), memory (p < 0.001), learning capacity (p < 0.001), spatial ability (p < 0.001), executive functions and attention (p < 0.001) 34 years after ALL treatment. Compared to controls ALL survivors had reduced white matter (WM) (492 vs 536 cm3, p < 0.001) and grey matter (GM) volumes (525 vs 555 cm3, p = 0.001). ALL survivors had lower levels of WM N-acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p = 0.004), WM NAA + NAAG (N-acetylaspartylglutamate)/Cr (1.61 vs 1.85, p < 0.001) and lower levels of GM NAA/Cr (1.18 vs 1.30, p = 0.001) and GM NAA + NAAG/Cr (1.28 vs 1.34, p = 0.01) compared to controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs 0.56, p = 0.01) concentrations compared to controls. There was a significantly negative correlation of years since ALL diagnosis to WM NAA + NAAG/Cr (r = −0.4, p = 0.04) in ALL survivors. The present study shows impaired brain metabolism detected by MRS, reduced brain volumes and neurocognitive impairment in childhood ALL survivors treated with cranial radiotherapy and chemotherapy, despite complete hormone substitution. We also report an impairment of metabolites correlated to time since treatment and a progressive impairment in sustained attention, suggesting an accelerated aging in the irradiated brain. Following these survivors many decades, or throughout life, after treatment with cranial radiotherapy and chemotherapy is highly warranted for a broader understanding of long-term outcome in this patient group.
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| 10. |
- Follin, Cecilia, et al.
(author)
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Microstructural white matter alterations associated to neurocognitive deficits in childhood leukemia survivors treated with cranial radiotherapy–a diffusional kurtosis study
- 2019
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In: Acta Oncologica. - 0284-186X. ; 58:7, s. 1021-1028
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Journal article (peer-reviewed)abstract
- Background: 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. Material and methods: 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. Results: ALL survivors scored lower than controls in neurocognitive tests of vocabulary, memory, learning capacity, spatial ability, executive functions, and attention (p <.001). The survivors had altered DTI parameters in the fornix, uncinate fasciculus, and ventral cingulum (all p <.05) and altered DKI parameters in the fornix, uncinate fasciculus, and dorsal and ventral cingulum (p <.05). Altered DTI parameters in the fornix were associated with impaired episodic verbal memory (r = −0.40, p <.04). The left and right uncinate fasciculus (r = 0.6, p <.001), (r = −0.5, p <.02) as well as the right ventral cingulum (r = 0.5, p <.007) were associated with impaired episodic visual memory. Altered DKI parameters in the fornix, right uncinate fasciculus (r = 0.3, r = 0.05, p =.02), and ventral cingulum (r = 0.3, p =.02) were associated with impaired results of episodic visual memory. Conclusion: 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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