About

The Laboratory of Mathematics in Imaging (LMI) is focused on the application of mathematical theory, analysis, modeling, and signal processing to medical imaging. Research projects within the group cover both novel theoretical contributions and translational clinical efforts. The research team combine strengths in computer science and mathematics with radiology, neuroscience, and novel MRI sequence developmentLearn more

Recent Publications

Associations Between Near End-of-Life Flortaucipir PET and Postmortem CTE-Related Tau Neuropathology in Six Former American Football Players

Alosco ML, Su Y, Stein TD, Protas H, Cherry JD, Adler CH, Balcer LJ, Bernick C, Pulukuri SV, Abdolmohammadi B, et al. Associations Between Near End-of-Life Flortaucipir PET and Postmortem CTE-Related Tau Neuropathology in Six Former American Football Players. Eur J Nucl Med Mol Imaging. 2022.Abstract
PURPOSE: Flourine-18-flortaucipir tau positron emission tomography (PET) was developed for the detection for Alzheimer's disease. Human imaging studies have begun to investigate its use in chronic traumatic encephalopathy (CTE). Flortaucipir-PET to autopsy correlation studies in CTE are needed for diagnostic validation. We examined the association between end-of-life flortaucipir PET and postmortem neuropathological measurements of CTE-related tau in six former American football players. METHODS: Three former National Football League players and three former college football players who were part of the DIAGNOSE CTE Research Project died and agreed to have their brains donated. The six players had flortaucipir (tau) and florbetapir (amyloid) PET prior to death. All brains from the deceased participants were neuropathologically evaluated for the presence of CTE. On average, the participants were 59.0 (SD = 9.32) years of age at time of PET. PET scans were acquired 20.33 (SD = 13.08) months before their death. Using Spearman correlation analyses, we compared flortaucipir standard uptake value ratios (SUVRs) to digital slide-based AT8 phosphorylated tau (p-tau) density in a priori selected composite cortical, composite limbic, and thalamic regions-of-interest (ROIs). RESULTS: Four brain donors had autopsy-confirmed CTE, all with high stage disease (n = 3 stage III, n = 1 stage IV). Three of these four met criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES). Two did not have CTE at autopsy and one of these met criteria for TES. Concomitant pathology was only present in one of the non-CTE cases (Lewy body) and one of the CTE cases (motor neuron disease). There was a strong association between flortaucipir SUVRs and p-tau density in the composite cortical (ρ = 0.71) and limbic (ρ = 0.77) ROIs. Although there was a strong association in the thalamic ROI (ρ = 0.83), this is a region with known off-target binding. SUVRs were modest and CTE and non-CTE cases had overlapping SUVRs and discordant p-tau density for some regions. CONCLUSIONS: Flortaucipir-PET could be useful for detecting high stage CTE neuropathology, but specificity to CTE p-tau is uncertain. Off-target flortaucipir binding in the hippocampus and thalamus complicates interpretation of these associations. In vivo biomarkers that can detect the specific p-tau of CTE across the disease continuum are needed.
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Association of War Zone-Related Stress With Alterations in Limbic Gray Matter Microstructure

Kaufmann E, Rojczyk P, Sydnor VJ, Guenette JP, Tripodis Y, Kaufmann D, Umminger L, Seitz-Holland J, Sollmann N, Rathi Y, et al. Association of War Zone-Related Stress With Alterations in Limbic Gray Matter Microstructure. JAMA Netw Open. 2022;5 (9) :e2231891.Abstract
Importance: Military service members returning from theaters of war are at increased risk for mental illness, but despite high prevalence and substantial individual and societal burden, the underlying pathomechanisms remain largely unknown. Exposure to high levels of emotional stress in theaters of war and mild traumatic brain injury (mTBI) are presumed factors associated with risk for the development of mental disorders. Objective: To investigate (1) whether war zone-related stress is associated with microstructural alterations in limbic gray matter (GM) independent of mental disorders common in this population, (2) whether associations between war zone-related stress and limbic GM microstructure are modulated by a history of mTBI, and (3) whether alterations in limbic GM microstructure are associated with neuropsychological functioning. Design, Setting, and Participants: This cohort study was part of the TRACTS (Translational Research Center for TBI and Stress Disorders) study, which took place in 2010 to 2014 at the Veterans Affair Rehabilitation Research and Development TBI National Network Research Center. Participants included male veterans (aged 18-65 years) with available diffusion tensor imaging data enrolled in the TRACTS study. Data analysis was performed between December 2017 to September 2021. Exposures: The Deployment Risk and Resilience Inventory (DRRI) was used to measure exposure to war zone-related stress. The Boston Assessment of TBI-Lifetime was used to assess history of mTBI. Stroop Inhibition (Stroop-IN) and Inhibition/Switching (Stroop-IS) Total Error Scaled Scores were used to assess executive or attentional control functions. Main Outcomes and Measures: Diffusion characteristics (fractional anisotropy of tissue [FAT]) of 16 limbic and paralimbic GM regions and measures of functional outcome. Results: Among 384 male veterans recruited, 168 (mean [SD] age, 31.4 [7.4] years) were analyzed. Greater war zone-related stress was associated with lower FAT in the cingulate (DRRI-combat left: P = .002, partial r = -0.289; DRRI-combat right: P = .02, partial r = -0.216; DRRI-aftermath left: P = .004, partial r = -0.281; DRRI-aftermath right: P = .02, partial r = -0.219), orbitofrontal (DRRI-combat left medial orbitofrontal cortex: P = .02, partial r = -0.222; DRRI-combat right medial orbitofrontal cortex: P = .005, partial r = -0.256; DRRI-aftermath left medial orbitofrontal cortex: P = .02, partial r = -0.214; DRRI-aftermath right medial orbitofrontal cortex: P = .005, partial r = -0.260; DRRI-aftermath right lateral orbitofrontal cortex: P = .03, partial r = -0.196), and parahippocampal (DRRI-aftermath right: P = .03, partial r = -0.191) gyrus, as well as with higher FAT in the amygdala-hippocampus complex (DRRI-combat: P = .005, partial r = 0.254; DRRI-aftermath: P = .02, partial r = 0.223). Lower FAT in the cingulate-orbitofrontal gyri was associated with impaired response inhibition (Stroop-IS left cingulate: P < .001, partial r = -0.440; Stroop-IS right cingulate: P < .001, partial r = -0.372; Stroop-IS left medial orbitofrontal cortex: P < .001, partial r = -0.304; Stroop-IS right medial orbitofrontal cortex: P < .001, partial r = -0.340; Stroop-IN left cingulate: P < .001, partial r = -0.421; Stroop-IN right cingulate: P < .001, partial r = -0.300; Stroop-IN left medial orbitofrontal cortex: P = .01, partial r = -0.223; Stroop-IN right medial orbitofrontal cortex: P < .001, partial r = -0.343), whereas higher FAT in the mesial temporal regions was associated with improved short-term memory and processing speed (left amygdala-hippocampus complex: P < .001, partial r = -0.574; right amygdala-hippocampus complex: P < .001, partial r = 0.645; short-term memory left amygdala-hippocampus complex: P < .001, partial r = 0.570; short-term memory right amygdala-hippocampus complex: P < .001, partial r = 0.633). A history of mTBI did not modulate the association between war zone-related stress and GM diffusion. Conclusions and Relevance: This study revealed an association between war zone-related stress and alteration of limbic GM microstructure, which was associated with cognitive functioning. These results suggest that altered limbic GM microstructure may underlie the deleterious outcomes of war zone-related stress on brain health. Military service members may benefit from early therapeutic interventions after deployment to a war zone.
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Evaluation of 137Cs, 133Xe and 3H Activity Concentrations Monitored in the Arctic Atmosphere

Zhang W, Paatero J, Leppänen A-P, Møller B, Jensen LK, Gudnason K, Sofiev M, Anderson Pål, Sickel M, Burakowska A, et al. Evaluation of 137Cs, 133Xe and 3H Activity Concentrations Monitored in the Arctic Atmosphere. J Environ Radioact. 2022;253-254 :107013.Abstract
This paper provides a brief introduction to the Arctic atmospheric radioactivity monitoring network. A decade of monitoring results have shown the 137Cs background levels in Arctic air range from 0.05 to 1.50 μBq/m3. The monitoring stations have sufficient sensitivity to detect 137Cs brought to the atmosphere due to resuspension in local soil and reemissions from biomass burning in a daily temporal resolution. These observations can be used as tracers for atmospheric processes. The 133Xe measurements obtained at Yellowknife, Resolute and Spitsbergen could support other research into how air pollution problems arise across intercontinental distances. It will help develop and improve models capable of predicting the long-distance transport and deposition of trace gases in the Arctic. Rainwater monitoring data collected in Finnish Lapland since the 1960's indicate that 3H radioactivity concentrations reached natural background levels in early 2000s, typically around 1-2 Bq/L monthly, with an annual seasonal variation cycle consistent with the observed of other cosmogenic radionuclides.
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Measures of Cortical Microstructure Are Linked to Amyloid Pathology in Alzheimer's Disease

Spotorno N, Strandberg O, Vis G, Stomrud E, Nilsson M, Hansson O. Measures of Cortical Microstructure Are Linked to Amyloid Pathology in Alzheimer's Disease. Brain. 2022.Abstract
Markers of downstream events are a key component of clinical trials of disease-modifying therapies for Alzheimer's disease. Morphological metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect Aβ-related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion-MRI can provide sensitive markers of cortical microstructural changes and to test their associations with multiple aspects of the Alzheimer's disease pathological cascade, including both Aβ and tau accumulation, astrocytic activation and cognitive deficits. We applied the mean apparent diffusion propagator model to diffusion-MRI data from 492 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER-2 cohort. Participants were stratified in Aβ-negative/tau-negative, Aβ-positive/tau-negative, and Aβ-positive/tau-positive based on Aβ- and tau-PET uptake. Cortical regional values of diffusion-MRI metrics and cortical thickness were compared across groups. Associations between regional values of diffusion-MRI metrics and both Aβ- and tau-PET uptake were also investigated along with the association with plasma level of glial fibrillary acidic protein (GFAP), a marker of astrocytes activation (available in 292 participants). Mean squared displacement revealed widespread microstructural differences already between Aβ-negative/tau-negative and Aβ-positive/tau-negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation. In contrast, differences in cortical thickness were clearly more limited. Mean squared displacement was also correlated with both Aβ- and tau-PET uptake even independently from one another and from cortical thickness. Further, the same metric exhibited significantly stronger correlations with PET uptake than cortical thickness (p < 0.05). Mean squared displacement was also positively correlated with GFAP with a pattern that resemble Aβ accumulation, and GFAP partially mediated the association between Aβ accumulation and mean squared displacement. Further, impairments in executive functions were significantly more associated with mean squared displacement values extracted from a meta-ROI encompassing regions accumulating Aβ early in the disease process, than with cortical thickness (p < 0.05). Similarly, impairments in memory functions were significantly more associated with mean squared displacement values extracted from a temporal meta-ROI, than with cortical thickness (p < 0.05). Metrics of cortical microstructural alteration derived from diffusion-MRI are highly sensitive to multiple aspects of the Alzheimer's disease pathological cascade. Of particular interest is the link with both Aβ-PET and GFAP suggesting diffusion-MRI might reflects microstructural changes related to the astrocytic response to Aβ aggregation. Therefore, metrics of cortical diffusion might be important outcome measures in anti-Aβ treatments clinical trials for detecting drug-induced changes in cortical microstructure.
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White Matter Degradation Near Cerebral Microbleeds Is Associated With Cognitive Change After Mild Traumatic Brain Injury

Irimia A, Ngo V, Chaudhari NN, Zhang F, Joshi SH, Penkova AN, O'Donnell LJ, Sheikh-Bahaei N, Zheng X, Chui HC. White Matter Degradation Near Cerebral Microbleeds Is Associated With Cognitive Change After Mild Traumatic Brain Injury. Neurobiol Aging. 2022;120 :68-80.Abstract
To explore how cerebral microbleeds (CMBs) accompanying mild traumatic brain injury (mTBI) reflect white matter (WM) degradation and cognitive decline, magnetic resonance images were acquired from 62 mTBI adults (imaged ∼7 days and ∼6 months post-injury) and 203 matched healthy controls. On average, mTBI participants had a count of 2.7 ± 2.6 traumatic CMBs in WM, located 6.1 ± 4.4 mm from cortex. At ∼6-month follow-up, 97% of CMBs were associated with significant reductions (34% ± 11%, q < 0.05) in the fractional anisotropy of WM streamlines within ∼1 cm of CMB locations. Male sex and older age were significant risk factors for larger reductions (q < 0.05). For CMBs in the corpus callosum, cingulum bundle, inferior and middle longitudinal fasciculi, fractional anisotropy changes were significantly and positively associated with changes in cognitive functions mediated by these structures (q < 0.05). Our findings distinguish traumatic from non-traumatic CMBs by virtue of surrounding WM alterations and challenge the assumption that traumatic CMBs are neurocognitively silent. Thus, mTBI with CMB findings can be described as a clinical endophenotype warranting longitudinal cognitive assessment.
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Pulmonary Arterial Pruning Is Associated With CT-Derived Bronchiectasis Progression in Smokers

Dolliver WR, Wang W, Nardelli P, Rahaghi FN, Orejas JL, Maselli DJ, Yen A, Young K, Kinney G, San José Estépar R, et al. Pulmonary Arterial Pruning Is Associated With CT-Derived Bronchiectasis Progression in Smokers. Respir Med. 2022;202 :106971.Abstract
Loss of small pulmonary arteries measured as the ratio of blood vessel volume in arteries <5 mm2 in cross-section to total arterial blood vessel volume (BV5a/TBVa), with lower values indicating more pruning, was associated with 5-yr progressing CT-derived bronchiectasis in smokers (Odds Ratio (OR) [95% Confidence interval], 1.28 [1.07-1.53] per 5% lower BV5a/TBVa, P = 0.007). Corresponding results in smokers with COPD were: OR 1.45 [1.11-1.89] per 5% lower BV5a/TBVa, P = 0.007. The results support a vascular factor for structural progression of bronchiectasis.
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