Diffusion Kurtosis Imaging Shows Similar Cerebral Axonal Damage in Patients with HIV Infection and Multiple Sclerosis

Buyukturkoglu, Korhan; Fleyser, Lazar; Byrd, Desiree; Morgello, Susan; Inglese, Matilde

doi:10.1111/jon.12497

Cited by 13 publications

(14 citation statements)

References 46 publications

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“…The above findings along with the observation of a strong positive correlation between HIV vDNA+ cells in the CC and GDS in virally suppressed subjects with HAND may suggest a potential role of HIV in the brain in the development of neurocognitive impairments despite suppressive long-term HAART. Brain imaging studies of HAART treated HIV patients have previously shown selective white matter disease (Garvey et al 2014; Ragin et al 2015; Randall et al 2017; Buyukturkoglu et al 2018) and a correlation between loss of CC integrity with neurocognitive deficits (Wu et al 2006; Kelly et al 2014). However, it is still unclear whether the neurocognitive impairment in the era of HAART is due to ART neurotoxicity or HIV induced neuroinflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy

Kang

Hattler

et al. 2018

J Neuroimmune Pharmacol

157

146

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The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and sustained viral suppression, as identified by the National NeuroAIDS Tissue Consortium. Using new, highly sensitive in situ hybridization techniques, RNAscope and DNAscope, in combination with immunohistochemistry, we were able to detect HIV-1 in the brains of all virally suppressed cases and found that brain macrophages and microglia, but not astrocytes, were the cells harboring HIV DNA in the brain. This study demonstrated that HIV reservoirs persist in brain macrophages/microglia during suppressive ART, which cure/treatment strategies will need to focus on targeting.

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Section: Discussionmentioning

confidence: 99%

Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy

Kang

Hattler

et al. 2018

J Neuroimmune Pharmacol

157

146

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“…DKI allows for the quantification of white matter tract integrity (WMTI), providing markers of intra‐axonal damage, axonal loss, extracellular inflammation, gliosis and demyelination . DKI‐derived metrics have been applied in several neurological disorders , providing increased sensitivity and specificity in detecting pathological changes .…”

Section: Introductionmentioning

confidence: 99%

Axonal water fraction as marker of white matter injury in primary‐progressive multiple sclerosis: a longitudinal study

Margoni

Petracca

Schiavi

et al. 2019

Euro J of Neurology

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Background and purpose Diffuse white matter (WM) injury is prominent in primary‐progressive multiple sclerosis (PP‐MS) pathology and is a potential biomarker of disease progression. Diffusion kurtosis imaging allows the quantification of non‐Gaussian water diffusion, providing metrics with high WM pathological specificity. The aim of this study was to characterize the pathological changes occurring in the normal‐appearing WM of patients with PP‐MS at baseline and at 1‐year follow‐up and to assess their impact on disability and short‐term disease progression. Methods A total of 26 patients with PP‐MS and 20 healthy controls were prospectively enrolled. Diffusion kurtosis imaging single‐shot echo‐planar imaging (EPI) was acquired on a 3‐T scanner (Philips Achieva, Best, The Netherlands) (voxel size, 2 × 2 × 2 mm3, 30 directions for each b‐value = 1000, 2000 s/mm2 and one b = 0 s/mm2). A two‐compartment biophysical model of WM tract integrity was used to derive spatial maps of axonal water fraction (AWF), intra‐axonal diffusivity, extra‐axonal axial and radial diffusivities (De,axial, De,radial) and tortuosity from the following WM tracts: corpus callosum (CC), corticospinal tract (CST) and posterior thalamic radiation (PTR). Results At baseline, patients with PP‐MS showed a widespread decrease of AWF, tortuosity and De,axial and an increase of De,radial in CC, CST and PTR (P ranging from 0.001 to 0.036). At 1‐year follow‐up, a significant AWF decrease was detected in the body of CC (P = 0.048), PTR (P = 0.008) and CST (P = 0.044). Baseline AWF values in CST significantly discriminated progressed from non‐progressed patients (P = 0.021; area under the curve, 0.854). Conclusion Based on its change over time and its relationship with disease progression, among the analyzed metrics, AWF seems the most sensitive metric of WM tissue damage in PP‐MS and therefore it could be considered as a marker for monitoring disease progression.

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“…Also, a recent study employed TBSS to compare normal appearing WM between HIV‐infected patients and multiple sclerosis patients to study associations between cognitive scores and WM tract integrity in two regions of interest (ROI) placed in the corpus callosum and ATR. While in our study, we employed a whole‐brain approach to correlational investigations, the ATR is comprised within the regions in which we found statistically significant associations between biochemical and DTI‐DKI metrics in the ATR . Also, this previous study did not exclude patients with coinfections, hence, introducing potential confounds which could have decreased the sensitivity of ROI‐wise correlational tests.…”

Section: Discussionmentioning

confidence: 98%

“…Also, this previous study did not exclude patients with coinfections, hence, introducing potential confounds which could have decreased the sensitivity of ROI‐wise correlational tests. While these finding could offer support for understanding physiopathological mechanism underlying the neurocognitive impairment of HIV patients, the pathogenesis of HIV‐related brain alterations remains in part unclear.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Multishell Diffusion Imaging Parameters are Associated with Blood Biomarkers of Disease Severity in HIV Infection

Garaci

Picchi

Giuliano

et al. 2019

Journal of Neuroimaging

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BACKGROUND AND PURPOSE: HIV-positive subjects suffer from neurocognitive deficits and disorder. We employ multishell diffusion imaging to investigate possible white matter microstructural correlates of infection severity, quantified through plasmatic percentage value of CD4 T-lymphocytes, Nadir-CD4 count, and plasma concentration of human immunodeficiency virus (HIV)-ribonucleic acid (RNA). METHODS: A total of 41 HIV patients underwent magnetic resonance imaging (MRI) and blood sampling to evaluate biochemical markers. Diffusion-weighted imaging was performed at 3 Tesla (b-values: 1000 s/mm² and 2500 s/mm², 64 gradient directions/bvalue, 8 b0 images). The Diffusion Tensor Imaging and Diffusional Kurtosis Imaging models were fitted separately after which mean, radial, and axial diffusivity (MD, RD, AD, respectively), fractional anistrotropy (FA), mean and radial kurtosis (MK and RK, respectively), and kurtosis anisotropy (KA) maps were extracted. Associations of each metric with biochemical markers were explored through tract-based spatial statistics followed by threshold-free cluster enhancement. RESULTS: We found significant positive associations between Nadir-CD4 values and both KA and FA, and significant negative associations between Nadir-CD4 values and MD. Also, we found significant positive associations among %CD4 and MK, KA, and FA, and significant negative associations among %CD4 values and MD. These associations were bilateral and involved predominantly the long association fibers. Anatomically, these associations were more widespread when using KA as compared to FA. No statistically significant associations with HIV-RNA concentrations were found. CONCLUSIONS:In HIV-positive subjects, associations between biochemical and diffusion-MRI variables are found along the association fibers, which connect brain areas involved in memory formation, providing a possible interpretation for the neurobiological substrate underlying cognitive disturbances in HIV.

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Diffusion Kurtosis Imaging Shows Similar Cerebral Axonal Damage in Patients with HIV Infection and Multiple Sclerosis

Cited by 13 publications

References 46 publications

Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy

Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy

Axonal water fraction as marker of white matter injury in primary‐progressive multiple sclerosis: a longitudinal study

Cerebral Multishell Diffusion Imaging Parameters are Associated with Blood Biomarkers of Disease Severity in HIV Infection

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