Tobias Granberg

Karolinska Institutet | KI · Department of Clinical Neuroscience

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T 1 /T 2-weighte...

Objective: In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with (11) C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appea...

Background and purpose: Quantitative MR imaging techniques are gaining interest as methods of reducing acquisition times while additionally providing robust measurements. This study aimed to implement a synthetic MR imaging method on a new scanner type and to compare its diagnostic accuracy and volumetry with conventional MR imaging in patients wi...

Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Altho...

Introduction: It is often challenging to clinically distinguish between Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Quantitative susceptibility mapping (QSM) is an accurate indirect method for estimating brain iron levels in vivo. This method has yet to be applied in atypical parkinsonism. We a...

Objective Systemic capillary leak syndrome (SCLS) is a rare condition associated with episodes of hypotension, hemoconcentration, hypoalbuminemia, and rhabdomyolysis. We describe a middle-aged man presenting with several distinct SCLS-like episodes, the last being fatal. In addition, in the year before the final event, he developed rapid cognitive...

Background: Virchow-Robin spaces (VRS) have been associated with neurodegeneration and neuroinflammation. However, it remains uncertain to what degree non-dilated or dilated VRS reflect specific features of neuroinflammatory pathology. Thus, we aimed at investigating the clinical relevance of VRS as imaging biomarker in multiple sclerosis (MS) and...

Background and objectives: Animal models for motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) are commonly used in preclinical research. However, it is insufficiently understood how much findings from these model systems can be translated to humans. Thus, we aimed at systematically assessing the translational value of MND an...

Background: The in vivo relation between microglia activation and demyelination in multiple sclerosis is still unclear. Objective: We combined 11C-PBR28 positron emission tomography and rapid estimation of myelin for diagnostic imaging (REMyDI) to characterize the relation between these pathological processes in a heterogeneous MS cohort. Metho...

Virchow-Robin spaces (VRS) have been associated with neurodegeneration and neuroinflammation. However, it remains uncertain to what degree non-dilated or dilated VRS reflect specific features of neuroinflammatory pathology. Thus, we aimed at investigating the clinical relevance of VRS as imaging biomarker in multiple sclerosis (MS) and to correlate...

Background and Purpose: Evidence of brain gadolinium retention has affected gadolinium-based contrast agent usage. It is, however, unclear towhat extentmacrocyclic agents are retained andwhether their in vivo detectionmay necessitate nonconventional MRI. Magnetization transfer (MT) could prove suitable to detect gadolinium-related signal changes si...

Background: Neurofilament light (NfL) levels reflect inflammatory disease activity in multiple sclerosis (MS), but it is less clear if NfL also can serve as a biomarker for MS progression in treated patients without relapses and focal lesion accrual. In addition, it has not been well established if clinically effective treatment re-establishes an a...

Background Most previous multiple sclerosis (MS) brain atrophy studies using MS impact scale 29 (MSIS-29) or symbol digit modalities test (SDMT) have been cross-sectional with limited sets of clinical outcomes. Objectives To investigate which brain and lesion volume metrics show the strongest long-term associations with the expanded disability sta...

Segmentation of Multiple Sclerosis (MS) lesions is a challenging problem. Several deep-learning-based methods have been proposed in recent years. However, most methods tend to be static, that is, a single model trained on a large, specialized dataset, which does not generalize well. Instead, the model should learn across datasets arriving sequentia...

Objectives The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation. Methods In a comprehensive literature search,...

Background: Dyspnea is common after COVID-19. Though the underlying mechanisms are largely unknown, lung perfusion abnormalities could contribute to lingering dyspnea. Objectives: To detect pulmonary perfusion disturbances in non-hospitalized individuals with post-COVID condition and persistent dyspnea 4-13 months after the disease onset. Metho...

Objective The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for dementia and Alzheimer's disease (AD), but the underlying mechanism for the increased risk is not well understood. Cerebral small vessel disease (SVD) is prevalent among patients with cognitive impairment and is thought to play an important role in the pathophysiolo...

Background: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and healthcare systems worldwide. An em...

Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare, genetic disease caused by heterozygous mutations in the CSF1R gene with rapidly progressive neurodegeneration, behavioral, cognitive, motor disturbances. Objective: To describe four cases of CSF1R-related leukoencephalopathy from three families with two different...

Background and purpose: Corpus callosum (CC) atrophy is a strong predictor of multiple sclerosis (MS) disability but the contributing pathological mechanisms remain uncertain. We aimed to apply advanced MRI to explore what drives the often nonuniform callosal atrophy. Methods: Prospective brain 7 Tesla and 3 Tesla Human Connectom Scanner MRI wer...

Background and purpose: Corpus callosum (CC) atrophy is predictive of future disability in multiple sclerosis (MS). However, current segmentation methods are either labor- or computationally intensive. We therefore developed an automated deep learning-based CC segmentation tool and hypothesized that its output would correlate with disability. Met...

Background Dyspnea is a prevalent symptom in the post-COVID-19 condition, though its mechanisms are largely unknown. Lung perfusion abnormalities have been reported in acute COVID-19 and could be suspected in patients with lingering dyspnea after the acute phase. Objectives To detect pulmonary perfusion disturbances in non-hospitalized post-COVID...

Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare but fatal microgliopathy. The diagnosis is often delayed due to multifaceted symptoms that can mimic several other neurological disorders. Imaging provides diagnostic clues that help identify cases. The objective of this study was to integrate the literature on neuro...

Background Neurocognitive manifestations of the coronavirus disease 2019 (COVID‐19) have been reported in the acute phase, especially in critically ill patients. The potential mechanisms underlying these symptoms are not fully understood but probably involves the inflammatory, vascular, and neurotropic effect of the coronavirus. While short‐, mid‐a...

Background: The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) such as amyotrophic lateral sclerosis (ALS) hampers the diagnostic utility of magnetic resonance imaging (MRI) in the clinical setting. Moreover, it is unknown how well MND animal models mimic actual human neuroimaging features. Objective: To perform...

Cortical demyelination occurs early in multiple sclerosis (MS) and relates to disease outcome. The brain cortex has endogenous propensity for remyelination as proven from histopathology study. In this study, we aimed at characterizing cortical microstructural abnormalities related to myelin content by applying a novel quantitative MRI technique in...

Background: Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare and devastating genetic disease caused by heterozygous mutations in the CSF1R gene. It is characterized by adult onset, rapidly progressive neurodegeneration and variable behavioral, cognitive, and motor disturbances and seizures. With only one affected f...

Introduction: We investigated the association between atrophy subtypes of Alzheimer's disease (AD), the ATN classification scheme, and key demographic and clinical factors in 2 cohorts with different source characteristics (a highly selective research-oriented cohort, the Alzheimer's Disease Neuroimaging Initiative [ADNI]; and a naturalistic heter...

SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusi...

Human T-lymphotropic virus type-1 (HTLV-1) is a neglected infection most often associated with an indolent process. However, a subset of HTLV-1 seropositive patients face the risk to develop life-threatening T-cell lymphoma/leukemia, or the highly disabling and incurable HTLV1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Over the y...

Background and purpose: Corpus callosum atrophy is a sensitive biomarker of multiple sclerosis (MS) neurodegeneration but typically requires manual 2D or volumetric 3D-based segmentations. We developed a supervised machine learning algorithm, DeepnCCA, for corpus callosum segmentation and relate callosal morphology to clinical disability using con...

Background Deep learning (DL) has provided impressive results in numerous domains in recent years, including medical image analysis. Training DL models requires large data sets to yield good performance. Since medical data can be difficult to acquire, most studies rely on public research cohorts, which often have harmonized scanning protocols and s...

Background Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. EPVS have been linked to small vessel disease. Some studies have also indicated an association of EPVS to neuroinflammation and/or neurodegeneration. However, there is...

Objective To perform a comprehensive characterization of a cohort of patients with congenital mirror movements (CMMs) in Sweden. Methods Clinical examination with the Woods and Teuber scale for mirror movements (MMs), neuroimaging, navigated transcranial magnetic stimulation (nTMS), and massive parallel sequencing (MPS) were applied. Results The...

Background: Brain metal homeostasis is essential for brain health, and deregulation can result in oxidative stress on the brain parenchyma. Objective: Our objective in this study was to focus on two hemorrhagic MRI manifestations of small vessel disease [cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS)] and associations with...

We used 7 T MRI to: (i) characterize the grey and white matter pathology in the cervical spinal cord of patients with early relapsing-remitting and secondary progressive multiple sclerosis; (ii) assess the spinal cord lesion spatial distribution and the hypothesis of an outside-in pathological process possibly driven by CSF-mediated immune cytotoxi...

In order to optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS-CoV-2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until July 26h...

To optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS‐CoV‐2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until 26 July 2020) usin...

Magnetic resonance imaging (MRI) is the most important paraclinical tool for assessing drug response in multiple sclerosis (MS) clinical trials. As such, MRI has also been widely used in preclinical research to investigate drug efficacy and pathogenic aspects in MS animal models. Keeping track of all published preclinical imaging studies, and possi...

Introduction Separating progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and multiple system atrophy (MSA) is often challenging in early disease but is important for appropriate management. Magnetic resonance imaging (MRI) can aid the diagnostics and manual 2D measurements are often used. However, new fully automatic brainstem vol...

Background Neurological complications in coronavirus disease 2019 (COVID-19) have been described, but the understanding of their pathophysiology and neuroanatomical correlates remains limited. Purpose To report on the frequency and type of neuroradiological findings in COVID-19. Materials and Methods In this retrospective study, all consecutive adu...

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions...

BACKGROUND We investigated the association between atrophy subtypes of Alzheimer’s disease (AD), the ATN classification scheme, and key demographic and clinical factors, in two cohorts with different source characteristics (a highly selective research-oriented cohort, ADNI; and a naturalistic heterogeneous clinically-oriented cohort, Karolinska Ima...

Objective To perform a comprehensive characterization of a cohort of patients with chorea-acanthocytosis (ChAc) in Sweden. Methods Clinical assessments, targeted genetic studies, neuroimaging with MRI, [ ¹⁸ F]-fluorodeoxyglucose (FDG) PET, and dopamine transporter with ¹²³ I FP-CIT (DaTscan) SPECT. One patient underwent magnetic resonance spectros...

SARS-CoV-2 enters the cell through the ACE2 receptor, which is considered one of the main inhibitors in the Renin-Angiotensin-Aldosterone System (RAAS).1 ,2 The virus has been shown to downregulate the ACE2 receptor, leading to a subsequent increase in the vasopressoragentangiotensinII.3 Evidently,criticalcoronavirusdisease2019(COVID-19)is thought...

SARS-CoV-2 enters the cell through the ACE2 receptor, which is considered one of the main inhibitors in the Renin-Angiotensin-Aldosterone System (RAAS).1 ,2 The virus has been shown to downregulate the ACE2 receptor, leading to a subsequent increase in the vasopressoragentangiotensinII.3 Evidently,criticalcoronavirusdisease2019(COVID-19)is thought...

Background: Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted...

Deep learning (DL) methods have in recent years yielded impressive results in medical imaging, with the potential to function as clinical aid to radiologists. However, DL models in medical imaging are often trained on public research cohorts with images acquired with a single scanner or with strict protocol harmonization, which is not representativ...

BACKGROUND AND PURPOSE Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and multiple sclerosis (MS) are demyelinating and neurodegenerative disorders that can be hard to distinguish clinically and radiologically. HDLS is a rare disorder compared to MS, which has led to occurrent misdiagnosis of HDLS as MS. That is problematic since thei...

Background Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted le...

Objective: The goal of this study was to characterize a Swedish family with members affected by spinocerebellar ataxia 27 (SCA27), a rare autosomal dominant disease caused by mutations in fibroblast growth factor 14 (FGF14). Despite normal structural neuroimaging psychiatric manifestations and intellectual disability are part of the SCA27 phenotyp...

Objective: MRI is essential for multiple sclerosis diagnostics but is not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex post-processing or lack of clinical approval. This study aimed to assess the specificity, robustness and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new mye...

Background and purpose: Corpus callosum atrophy is a neurodegenerative biomarker in multiple sclerosis (MS). Manual delineations are gold standard but subjective and labor intensive. Novel automated methods are promising but require validation. We aimed to compare the robustness of manual versus automatic corpus callosum segmentations based on Fre...

Deep learning (DL) methods have in recent years yielded impressive results in medical imaging, with the potential to function as clinical aid to radiologists. However, DL models in medical imaging are often trained on public research cohorts with images acquired with a single scanner or with strict protocol harmonization, which is not representativ...

Objectives: To determine if treatment with autologous hematopoietic stem cell transplantation can induce sustained complete remission in patients with multiple sclerosis (MS). Material and methods: Case series of patients with relapsing-remitting MS (n=10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patient...

Background and purpose: Brain gadolinium retention is consistently reported for linear gadolinium-based contrast agents, while the results for macrocyclics are contradictory and potential clinical manifestations remain controversial. Furthermore, most previous studies are based on conventional T1-weighted MR imaging. We therefore aimed to quantita...

Rituximab, a chimeric anti-CD20-antibody, attracts increasing attention as a treatment option for multiple sclerosis (MS). Apart from smaller controlled trials, an increasing number of studies in real-world populations indicate high efficacy based on clinical and neuroradiological outcomes for rituximab in relapsing-remitting MS patients. Additiona...