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Fällmar, David
Publications (10 of 11) Show all publications
Finnsson, J., Lubberink, M., Savitcheva, I., Fällmar, D., Melberg, A., Kumlien, E. & Raininko, R. (2019). Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.. Acta Neurologica Scandinavica, 139(2), 135-142
Open this publication in new window or tab >>Glucose metabolism in the brain in LMNB1-related autosomal dominant leukodystrophy.
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2019 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 139, no 2, p. 135-142Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: LMNB1-related autosomal dominant leukodystrophy is caused by an overexpression of the protein lamin B1, usually due to a duplication of the LMNB1 gene. Symptoms start in 5th to 6th decade. This slowly progressive disease terminates with death. We studied brain glucose metabolism in this disease using 18 F-fluorodeoxyglucose positron emission tomography (PET).

METHODS: We examined 8 patients, aged 48-64 years, in varying stages of clinical symptomatology. Two patients were investigated with quantitative PET on clinical indications after which six more patients were recruited. Absolute glucose metabolism was analyzed with the PVElab software in 6 patients and 18 healthy controls. A semiquantitative analysis using the CortexID software was performed in seven investigations, relating local metabolism levels to global glucose metabolism.

RESULTS: The clinical quantitative PET revealed low global glucose metabolism, with the most marked reduction in the cerebellum. In the PVElab analysis, patients presented low mean glucose metabolism in the cerebellum, brainstem and global grey matter. In the semiquantitative analysis, 2 patients showed a decreased metabolism in the cerebellum and 4 patients a relatively higher metabolism in parts of the temporal lobes. Since none of the patients showed an increased metabolism in the quantitative analysis, we interpret these increases as "pseudo-increases" related to a globally reduced metabolism.

CONCLUSIONS: Global reduction of grey matter glucose metabolism in this white matter disease most likely depends on a combination of cortical afferent dysfunction and, in later stages, neuronal loss. The lowest metabolism in the cerebellum is consistent with histopathological findings and prominent cerebellar symptoms.

Keywords
18F-fluorodeoxyglucose, adult-onset leukodystrophy, autosomal dominant leukodystrophy, glucose metabolism, positron emission tomography
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-362200 (URN)10.1111/ane.13024 (DOI)000454813600005 ()30192380 (PubMedID)
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2019-01-30Bibliographically approved
Persson, J., Szalisznyo, K., Antoni, G., Wall, A., Fällmar, D., Zora, H. & Bodén, R. (2019). Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study. European Archives of Psychiatry and Clinical Neuroscience
Open this publication in new window or tab >>Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study
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2019 (English)In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491Article in journal (Refereed) Published
Abstract [en]

Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.

National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:uu:diva-392015 (URN)10.1007/s00406-019-01021-0 (DOI)
Available from: 2019-08-28 Created: 2019-08-28 Last updated: 2019-08-28Bibliographically approved
Lubberink, M., Widström, C., Jonasson, M., Appel, L., Fällmar, D., Nyholm, D., . . . Danfors, T. (2018). Differential diagnosis of patients with parkinsonian syndrome using multilinear regression to disease-specific C-11-PE2I-PET templates and classification tree learning. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S409-S409
Open this publication in new window or tab >>Differential diagnosis of patients with parkinsonian syndrome using multilinear regression to disease-specific C-11-PE2I-PET templates and classification tree learning
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S409-S409Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372967 (URN)000449266204001 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
Fällmar, D., Lilja, J., Danfors, T., Kilander, L., Iyer, V., Lubberink, M., . . . Sörensen, J. (2018). Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.. American Journal of Nuclear Medicine and Molecular Imaging, 8(4), 239-246
Open this publication in new window or tab >>Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.
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2018 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 8, no 4, p. 239-246Article in journal (Refereed) Published
Abstract [en]

Neuroimaging is a central part of diagnostic work-up of patients with suspected neurodegenerative disease. FDG-PET can reveal pathological changes earlier and more reliably than morphological imaging. Diagnostic accuracy can be improved by constructing 3D SSP Z-score maps, showing patterns of significant deficits. During FDG-PET, the subject receives a moderate but not insignificant dose of ionizing radiation, and a dose reduction with retained image quality is desirable. With lower dose, repeated examinations can become a useful tool for monitoring disease progress and potential effects of disease-modifying interventions. The aim of this study was to evaluate Z-maps created from low-dose and normal-dose FDG-PET of the brain, with quantitative and qualitative methods. Nine patients with neurodegenerative disorders were prospectively enrolled and nine age-matched controls were recruited through advertising. All subjects (n=18) underwent two FDG-PET scans on separate occasions; a routine and a low-dose scan. The routine dosage of FDG was 3 MBq/kg, and low dosage was 0.75 MBq/kg. 3D-SSP images showing Z-scores of < -1.96 were created from 10-minute summations. The study was comprised of a quantitative part comparing the Z-scores, and a qualitative part where experienced nuclear medicine specialists visually assessed the images. Regarding the quantitative part, Bland-Altman analysis showed a slight constant bias (0.206). Regarding qualitative discrimination between patients and controls, the performance between normal- and low-dose were equal, both showing 72% sensitivity, 83% specificity and 78% accuracy. In this study, visual assessment of 3D-SSP Z-score maps from low-dose FDG-PET provided diagnostic information highly comparable to normal-dose, with minor quantitative discrepancies.

Keywords
FDG, PET, methodology, neurodegeneration, neuroimaging, radiation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-362198 (URN)000444491000001 ()30245916 (PubMedID)
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2018-11-15Bibliographically approved
Fällmar, D., Haller, S., Lilja, J., Danfors, T., Kilander, L., Tolboom, N., . . . Larsson, E.-M. (2017). Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.. European Radiology, 27(10), 4237-4246
Open this publication in new window or tab >>Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.
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2017 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 27, no 10, p. 4237-4246Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.

METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.

RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168).

CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.

KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

Keywords
18F-FDG, Arterial spin labeling MRI, Dementia, Neurodegenerative, Visual assessment
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-319602 (URN)10.1007/s00330-017-4784-1 (DOI)000408952400027 ()28374078 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2018-01-03Bibliographically approved
Shams, S., Fällmar, D., Schwarz, S., Wahlund, L.-O., van Westen, D., Hansson, O., . . . Haller, S. (2017). MRI of the Swallow Tail Sign: A Useful Marker in the Diagnosis of Lewy Body Dementia?. American Journal of Neuroradiology, 38(9), 1737-1741
Open this publication in new window or tab >>MRI of the Swallow Tail Sign: A Useful Marker in the Diagnosis of Lewy Body Dementia?
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2017 (English)In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 38, no 9, p. 1737-1741Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: There are, to date, no MR imaging diagnostic markers for Lewy body dementia. Nigrosome 1, containing dopaminergic cells, in the substantia nigra pars compacta is hyperintense on SWI and has been called the swallow tail sign, disappearing with Parkinson disease. We aimed to study the swallow tail sign and its clinical applicability in Lewy body dementia and hypothesized that the sign would be likewise applicable in Lewy body dementia.

MATERIALS AND METHODS: This was a retrospective cross-sectional multicenter study including 97 patients (mean age, 65 ± 10 years; 46% women), consisting of the following: controls (n = 21) and those with Lewy body dementia (n = 19), Alzheimer disease (n = 20), frontotemporal lobe dementia (n = 20), and mild cognitive impairment (n = 17). All patients underwent brain MR imaging, with susceptibility-weighted imaging at 1.5T (n = 46) and 3T (n = 51). The swallow tail sign was assessed independently by 2 neuroradiologists.

RESULTS: Interrater agreement was moderate (κ = 0.4) between raters. An abnormal swallow tail sign was most common in Lewy body dementia (63%; 95% CI, 41%-85%; P < .001) and had a predictive value only in Lewy body dementia with an odds ratio of 9 (95% CI, 3-28; P < .001). The consensus rating for Lewy body dementia showed a sensitivity of 63%, a specificity of 79%, a negative predictive value of 89%, and an accuracy of 76%; values were higher on 3T compared with 1.5T. The usefulness of the swallow tail sign was rater-dependent with the highest sensitivity equaling 100%.

CONCLUSIONS: The swallow tail sign has diagnostic potential in Lewy body dementia and may be a complement in the diagnostic work-up of this condition.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-327245 (URN)10.3174/ajnr.A5274 (DOI)000409827200016 ()28705819 (PubMedID)
Funder
Stockholm County CouncilThe Karolinska Institutet's Research FoundationThe Dementia Association - The National Association for the Rights of the Demented
Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2017-12-06Bibliographically approved
Haller, S., Fällmar, D. & Larsson, E.-M. (2016). Susceptibility weighted imaging in dementia with Lewy bodies: will it resolve the blind spot of MRI? [Letter to the editor]. Neuroradiology, 58(2), 217-218
Open this publication in new window or tab >>Susceptibility weighted imaging in dementia with Lewy bodies: will it resolve the blind spot of MRI?
2016 (English)In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 58, no 2, p. 217-218Article in journal, Letter (Refereed) Published
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-266414 (URN)10.1007/s00234-015-1605-6 (DOI)000371413300015 ()26458890 (PubMedID)
Available from: 2015-11-09 Created: 2015-11-09 Last updated: 2017-12-01Bibliographically approved
Fällmar, D., Lilja, J., Kilander, L., Danfors, T., Lubberink, M., Larsson, E.-M. & Sörensen, J. (2016). Validation of true low-dose 18F-FDG PET of the brain. American Journal of Nuclear Medicine and Molecular Imaging, 6(5), 269-276
Open this publication in new window or tab >>Validation of true low-dose 18F-FDG PET of the brain
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2016 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 5, p. 269-276Article in journal (Refereed) Published
Abstract [en]

The dosage of 18F-FDG must be sufficient to ensure adequate PET image quality. For younger patients and research controls, the lowest possible radiation dose should be used. The purpose of this study was to find a protocol for FDG-PET of the brain with reduced radiation dose and preserved quantitative characteristics. Eight patients with neurodegenerative disorders and nine controls (n=17) underwent FDG-PET/CT twice on separate occasions, first with normal-dose (3 MBq/kg), and second with low-dose (0.75 MBq/kg, 25% of the original). Five additional controls (total n=22) underwent FDG-PET twice, using normal-dose and ultra-low-dose (0.3 MBq/kg, 10% of original). All subjects underwent MRI. Ten-minute summation images were spatially normalized and intensity normalized. Regional standard uptake value ratios (SUV-r) were calculated using an automated atlas. SUV-r values from the normal- and low-dose images were compared pairwise. No clinically significant bias was found in any of the three groups. The mean absolute difference in regional SUV-r values was 0.015 (1.32%) in controls and 0.019 (1.67%) in patients. The ultra-low-dose protocol produced a slightly higher mean difference of 0.023 (2.10%). The main conclusion is that 0.75 MBq/kg (56 MBq for a 75-kg subject) is a sufficient FDG dose for evaluating regional SUV-ratios in brain PET scans in adults with or without neurodegenerative disease, resulting in a reduction of total PET/CT effective dose from 4.54 to 1.15 mSv. The ultra-low-dose (0.5 mSv) could be useful in research studies requiring serial PET in healthy controls or children.

Place, publisher, year, edition, pages
Madison, USA: e-Century Publishing Corporation, 2016
Keywords
PET, FDG, neuroimaging, neurodegeneration, methodology, Hjärnavbildning, PET, lågdos, demens, neurodegenerativ
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Radiology
Identifiers
urn:nbn:se:uu:diva-304730 (URN)
Available from: 2016-10-08 Created: 2016-10-08 Last updated: 2017-11-30Bibliographically approved
Fällmar, D., Lilja, J., Kilander, L., Danfors, T., Lubberink, M., Larsson, E.-M. & Sörensen, J. (2016). Validation of true low-dose 18F-FDG PET of the brain. American Journal of Nuclear Medicine and Molecular Imaging, 6(5), 269-276
Open this publication in new window or tab >>Validation of true low-dose 18F-FDG PET of the brain
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2016 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 6, no 5, p. 269-276Article in journal (Refereed) Published
Abstract [en]

The dosage of F-18-FDG must be sufficient to ensure adequate PET image quality. For younger patients and research controls, the lowest possible radiation dose should be used. The purpose of this study was to find a protocol for FDG-PET of the brain with reduced radiation dose and preserved quantitative characteristics. Eight patients with neurodegenerative disorders and nine controls (n= 17) underwent FDG-PET/ CT twice on separate occasions, first with normal-dose (3 MBq/ kg), and second with low-dose (0.75 MBq/ kg, 25% of the original). Five additional controls (total n= 22) underwent FDG-PET twice, using normal-dose and ultra-low-dose (0.3 MBq/ kg, 10% of original). All subjects underwent MRI. Ten-minute summation images were spatially normalized and intensity normalized. Regional standard uptake value ratios (SUV-r) were calculated using an automated atlas. SUV-r values from the normal-and low-dose images were compared pairwise. No clinically significant bias was found in any of the three groups. The mean absolute difference in regional SUV-r values was 0.015 (1.32%) in controls and 0.019 (1.67%) in patients. The ultra-low-dose protocol produced a slightly higher mean difference of 0.023 (2.10%). The main conclusion is that 0.75 MBq/ kg (56 MBq for a 75-kg subject) is a sufficient FDG dose for evaluating regional SUV-ratios in brain PET scans in adults with or without neurodegenerative disease, resulting in a reduction of total PET/ CT effective dose from 4.54 to 1.15 mSv. The ultra-low-dose (0.5 mSv) could be useful in research studies requiring serial PET in healthy controls or children.

Keywords
PET, FDG, neuroimaging, neurodegeneration, methodology
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-329550 (URN)000398121600003 ()27766185 (PubMedID)
Available from: 2017-11-17 Created: 2017-11-17 Last updated: 2019-04-08
Fällmar, D., Lilja, J., Velickaite, V., Danfors, T., Lubberink, M., Ahlgren, A., . . . Larsson, E.-M. (2016). Visual Assessment of Brain Perfusion MRI Scans in Dementia: a Pilot Study. Journal of Neuroimaging, 26(3), 324-330
Open this publication in new window or tab >>Visual Assessment of Brain Perfusion MRI Scans in Dementia: a Pilot Study
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2016 (English)In: Journal of Neuroimaging, ISSN 1051-2284, E-ISSN 1552-6569, Vol. 26, no 3, p. 324-330Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Functional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG-PET data.

METHODS: Ten patients with a clinical diagnosis of dementia and 11 age-matched cognitively healthy controls were examined with pseudo-continuous ASL (pCASL) and 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Three diagnostic physicians visually assessed the pCASL maps after subtraction only, and after postprocessing using Gaussian smoothing and GLM-based beta estimate functions. The assessment scores were compared to FDG PET values. Furthermore, the ability to discriminate patients from healthy elderly controls was assessed.

RESULTS: Smoothing improved the correlation between visually assessed regional ASL perfusion scores and the FDG PET SUV-r values from the corresponding regions. However, subtracted pCASL maps discriminated patients from healthy controls better than smoothed maps. Smoothing increased the number of false-positive patient identifications. Application of beta estimate functions had only a marginal effect.

CONCLUSION: Spatial smoothing of ASL images increased false positive results in the discrimination of hypoperfusion conditions from healthy elderly. It also decreased interreader agreement. However, regional characterization and subjective perception of image quality was improved.

Keywords
Arterial spin labeling; smoothing; visual assessment; brain perfusion; clinical setting
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-266305 (URN)10.1111/jon.12296 (DOI)000382869200012 ()26376736 (PubMedID)
Available from: 2015-11-06 Created: 2015-11-06 Last updated: 2017-12-01Bibliographically approved
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