Imaging of Brain Structural and Functional Effects in People With Human Immunodeficiency Virus.

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting "Biotypes of CNS Complications in People Living with HIV," held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

Legacy effect on neuropsychological function in HIV-infected men on combination antiretroviral therapy.

OBJECTIVE: To determine whether combination antiretroviral therapy (cART) initiation alters the trajectory of cognitive performance in HIV+ men, and whether cognition prior to cART predicts postcART function. DESIGN: Longitudinal cohort study. Multicenter AIDS Cohort Study. METHODS: From an initial set of 3701 men with complete neuropsychological data, men with HIV infection were initially matched with men without infection on cognitive status, race, age, and timeline (T0 defined as cART initiation). Propensity score matching was then used to match pairs on depressive symptoms at T0, education, T0 cognitive scores, and recruitment cohort. There were 506 matched pairs of infected and uninfected men in the final analysis. Mixed effect models were constructed to analyze the trajectories of cognitive functions and to test the effect of cART and HIV on cognitive functions over time. RESULTS: Performance in each cognitive domain did not change following the initiation of cART among HIV-infected men with prior impairment and was comparable to the performance of their matched uninfected men. However, among the infected men who were unimpaired prior to cART, motor function declined significantly faster than it did for uninfected controls. CONCLUSIONS: Cognitive dysfunction is persistent in HIV-infected men and cART does not alter the trajectory of cognitive decline in men who were impaired prior to effective therapy. This suggests that current cognitive impairment in HIV+ men results from a legacy effect, and from factors other than the HIV itself. Furthermore, motor skills may be uniquely vulnerable to the virus, cART, or age-related co-morbidities.

Longitudinal 5-year prediction of cognitive impairment among men with HIV disease.

BACKGROUND: Although combination antiretroviral therapy reduced the prevalence of HIV-associated dementia, milder syndromes persist. Our goals were to predict cognitive impairment of the Multicenter AIDS Cohort Study (MACS) participants 5 years ahead and from a large pool of factors, select the ones that mostly contributed to our predictions. DESIGN: Longitudinal, natural and treated history of HIV infection among MSM. METHODS: The MACS is a longitudinal study of the natural and treated history of HIV disease in MSM; the neuropsychological substudy aims to characterize cognitive disorders in men with HIV disease. RESULTS: We modeled on an annual basis the risk of cognitive impairment 5 years in the future. We were able to predict cognitive impairment at individual level with high precision and overperform default methods. We found that while a diagnosis of AIDS is a critical risk factor, HIV infection per se does not necessarily convey additional risk. Other infectious processes, most notably hepatitis B and C, are independently associated with increased risk of impairment. The relative importance of an AIDS diagnosis diminished across calendar time. CONCLUSION: Our prediction models are a powerful tool to help clinicians address dementia in early stages for MACS paticipants. The strongest predictors of future cognitive impairment included the presence of clinical AIDS and hepatitis B or C infection. The fact that the pattern of predictive power differs by calendar year suggests a clinically critical change to the face of the epidemic.

Evaluation of image quality of wideband single-shot late gadolinium-enhancement MRI in patients with a cardiac implantable electronic device.

INTRODUCTION: While wideband segmented, breath-hold late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) has been shown to suppress image artifacts associated with cardiac-implanted electronic devices (CIEDs), it may produce image artifacts in patients with arrhythmia and/or dyspnea. Single-shot LGE is capable of suppressing said artifacts. We sought to compare the performance of wideband single-shot free-breathing LGE against the standard and wideband-segmented LGEs in CIED patients. METHODS AND RESULTS: We retrospectively identified all 54 consecutive patients (mean age: 61 ± 15 years; 31% females) with CIED who had undergone CMR with standard segmented, wideband segmented, and/or wideband single-shot LGE sequences as part of quality assurance for determining best clinical practice at 1.5 T. Two raters independently graded the conspicuity of myocardial scar or normal myocardium and the presence of device artifact level on a 5-point Likert scale (1: worst; 3: acceptable; 5: best). Summed visual score (SVS) was calculated as the sum of conspicuity and artifact scores (SVS ≥ 6 defined as diagnostically interpretable). Median conspicuity and artifact scores were significantly better for wideband single-shot LGE (F = 24.2, p < .001) and wideband-segmented LGE (F = 20.6, p < .001) compared to standard-segmented LGE. Among evaluated myocardial segments, 72% were deemed diagnostically interpretable-defined as SVS ≥ 6-for standard-segmented LGE, 89% were deemed diagnostically interpretable for wideband-segmented LGE, and 94% segments were deemed diagnostically interpretable for wideband single-shot LGE. CONCLUSIONS: Wideband single-shot LGE and wideband-segmented LGE produced similarly improved image quality compared to standard LGE.

Left ventricular extracellular volume expansion does not predict recurrence of atrial fibrillation following catheter ablation.

INTRODUCTION: A recent study reported that diffuse left ventricular (LV) fibrosis is a predictor of atrial fibrillation (AF) recurrence following catheter ablation, by measuring postcontrast cardiac T1 (an error prone metric as per the 2017 Society for Cardiovascular Magnetic Resonance consensus statement) using an inversion-recovery pulse sequence (an error prone method in arrhythmia) in AF ablation candidates. The purpose of this study was to verify the prior study, by measuring extracellular volume (ECV) fraction (an accurate metric) using a saturation-recovery pulse sequence (accurate method in arrhythmia). METHODS AND RESULTS: This study examined 100 AF patients (mean age = 62 ± 11 years, 69 males and 31 females, 67 paroxysmal [pAF] and 33 persistent [peAF]) who underwent a preablation cardiovascular magnetic resonance (CMR) exam. LV ECV and left atrial (LA) and LV functional parameters were quantified using standard analysis methods. During an average follow-up period of 457 ± 261 days with 4 ± 3 rhythm checks per patient, 72 patients maintained sinus rhythm. Between those who maintained sinus rhythm (n = 72) and those who reverted to AF (n = 28), the only clinical characteristic that was significantly different was age (60 ± 12 years vs 66 ± 9 years); for CMR metrics, neither mean LV ECV (25.1 ± 3.3% vs 24.7 ± 3.7%), native LV T1 (1093.8 ± 73.5 ms vs 1070.2 ± 115.9 ms), left ventricular ejection fraction (54.1 ± 11.2% vs 55.7 ± 7.1%), nor LA end diastolic volume/body surface area (42.4 ± 14.8 mL/m2 vs 43.4 ± 19.6 mL/m2 ) were significantly different (P ≥ .23). According to Cox regression tests, none of the clinical and imaging variables predict AF recurrence. CONCLUSION: Neither LV ECV nor other CMR metrics predict recurrence of AF following catheter ablation.

Accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, compressed sensing, and k-space weighted image contrast reconstruction tailored for visual analysis and quantification of myocardial blood flow.

PURPOSE: To develop an accelerated cardiac perfusion pulse sequence and test whether it is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of myocardial blood flow (MBF). METHODS: We implemented an accelerated first-pass cardiac perfusion pulse sequence by combining radial k-space sampling, compressed sensing (CS), and k-space weighted image contrast (KWIC) filtering. The proposed and clinical standard pulse sequences were evaluated in a randomized order in 13 patients at rest. For visual analysis, 3 readers graded the conspicuity of wall enhancement, artifact, and noise level on a 5-point Likert scale (overall score index = sum of 3 individual scores). Resting MBF was calculated using a Fermi function model with and without KWIC filtering. Mean visual scores and MBF values were compared between sequences using appropriate statistical tests. RESULTS: The proposed pulse sequence produced greater spatial coverage (6-8 slices) with higher spatial resolution (1.6 × 1.6 × 8 mm3 ) and shorter readout duration (78 ms) compared to clinical standard (3-4 slices, 3 × 3 × 8 mm3 , 128 ms, respectively). The overall image score index between accelerated (11.1 ± 1.3) and clinical standard (11.2 ± 1.3) was not significantly different (P = 0.64). Mean resting MBF values with KWIC filtering (0.9-1.2 mL/g/min across different slices) were significantly lower (P < 0.0001) than those without KWIC filtering (3.1-4.3 mL/g/min) and agreed better with values reported in literature. CONCLUSION: An accelerated, first-pass cardiac perfusion pulse sequence with radial k-space sampling, CS, and KWIC filtering is capable of increasing spatial coverage, generating high-quality images, and enabling quantification of MBF.

Analysis of the RENAL and mRENAL Scores and the Relative Importance of Their Components in the Prediction of Complications and Local Progression after Percutaneous Renal Cryoablation.

PURPOSE: To determine if modified RENAL (mRENAL) score and its individual components have superior predictive value relative to the RENAL nephrometry score in prediction of complications and recurrence after percutaneous renal cryoablation. MATERIALS AND METHODS: Primary masses treated with CT-guided percutaneous renal cryoablation between June 2007 and May 2016 were retrospectively reviewed. RENAL and mRENAL scores were used to stratify masses into low, medium, and high complexity tertiles. Complications were characterized by SIR criteria. Predictors of complications and local progression were analyzed using multivariate logistic regression and Kaplan-Meier analysis. RESULTS: There were 95 renal cryoablation procedures in 86 patients. Of ablations, 89 had at least 1 follow-up imaging study, with median follow-up of 29 months. There were 11 (12.4%) complications, including 5 (6.5%) major complications. Mass complexity, as measured by mRENAL complexity tertile, was associated with increased risk of complications on multivariate analysis (P = .045). Endophytic location was the only individual ordinal component of the RENAL and mRENAL scores associated with complications (P = .021). Local progression occurred in 7 (8.3%) masses. Complexity as measured by either scoring system was not associated with local progression. Only diameter > 3 cm was associated with increased risk of local progression (hazard ratio = 9.9, 95% confidence interval = 2.1-45, P = .003). CONCLUSIONS: mRENAL score was predictive of complications and tumor size was predictive of recurrence. Use of mRENAL score for complications and tumor size for recurrence should allow for simpler risk stratification and more accurate patient counseling.

Cognitive function in early HIV infection.

This study aimed to examine cognitive function in acute/early HIV infection over the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants of the Chicago Early HIV Infection Study were evaluated using a comprehensive neuropsychological assessment at study enrollment and at 2-year follow-up. Cognitive performance measures were compared in the groups using t tests and mixed-effect models. Patterns of relationship with clinical measures were determined between cognitive function and clinical status markers using Spearman's correlations. At the initial timepoint, the HIV group demonstrated significantly weaker performance on measures of verbal memory, visual memory, psychomotor speed, motor speed, and executive function. A similar pattern was found when cognitive function was examined at follow-up and across both timepoints. The HIV subjects had generally weaker performance on psychomotor speed, executive function, motor speed, visual memory, and verbal memory. The rate of decline in cognitive function across the 2-year follow-up period did not differ between groups. Correlations between clinical status markers and cognitive function at both timepoints showed weaker performance associated with increased disease burden. Neurocognitive difficulty in chronic HIV infection may have very early onset and reflect consequences of initial brain viral invasion and neuroinflammation during the intense, uncontrolled viremia of acute HIV infection. Further characterization of the changes occurring in initial stages of infection and the risk and protective factors for cognitive function could inform new strategies for neuroprotection.

Brain alterations within the first 100 days of HIV infection.

OBJECTIVE: Brain involvement is a serious complication of HIV infection. The earliest changes in the brain, which represents an anatomic site for viral persistence, are largely unknown. METHODS: This investigation used quantitative Magnetic Resonance methodologies, including high resolution and diffusion tensor (DTI) imaging, to evaluate the brain in 15 HIV and 20 seronegative subjects. All HIV subjects were antibody nonreactive with assay-estimated infection duration of less than 100 days. RESULTS: Brain volumetric analysis revealed reduced parenchyma with enlargement of the third ventricle and brainstem. DTI quantified loss of white matter integrity in the corpus callosum and diffusion alterations in caudate. Cognitive differences were indicated in psychomotor speed and visual recall. There were no differences between antiretroviral-initiated and naïve HIV subgroups. INTERPRETATION: These findings, quantified within 100 days of infection, shed light on the earliest brain changes in HIV infection. Onset of neural injury may date to initial viral invasion and the transient early period of unchecked viremia and marked immunosuppression of the seroconversion period.

Identifying HIV-induced subgraph patterns in brain networks with side information.

Investigating brain connectivity networks for neurological disorder identification has attracted great interest in recent years, most of which focus on the graph representation alone. However, in addition to brain networks derived from the neuroimaging data, hundreds of clinical, immunologic, serologic, and cognitive measures may also be documented for each subject. These measures compose multiple side views encoding a tremendous amount of supplemental information for diagnostic purposes, yet are often ignored. In this paper, we study the problem of subgraph selection from brain networks with side information guidance and propose a novel solution to find an optimal set of subgraph patterns for graph classification by exploring a plurality of side views. We derive a feature evaluation criterion, named gSide, to estimate the usefulness of subgraph patterns based upon side views. Then we develop a branch-and-bound algorithm, called gMSV, to efficiently search for optimal subgraph patterns by integrating the subgraph mining process and the procedure of discriminative feature selection. Empirical studies on graph classification tasks for neurological disorders using brain networks demonstrate that subgraph patterns selected by the multi-side-view-guided subgraph selection approach can effectively boost graph classification performances and are relevant to disease diagnosis.

Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum.

The purpose of this study was to examine the impact of early suppressive antiretroviral therapy (ART) on brain structure and neurocognitive outcomes. We conducted an observational study of subjects within 1 year of HIV infection. Ten ART-naïve and 10 ART-suppressed individuals were matched for age and infection duration and age-matched to 10 HIV-seronegative controls. Quantitative brain imaging and neurocognitive data were analyzed. Subjects on suppressive ART had diminished corpus callosum structural integrity on macromolecular and microstructural imaging, higher cerebrospinal fluid percent, higher depression scores, and lower functional performance. Early suppressive ART may alter the trajectory of neurological progression of HIV infection, particularly in the corpus callosum.

MR imaging enables measurement of therapeutic nanoparticle uptake in rat N1-S1 liver tumors after nanoablation.

PURPOSE: To test the hypothesis that magnetic resonance (MR) imaging can quantify intratumoral superparamagnetic iron oxide (SPIO) nanoparticle uptake after nanoablation. MATERIALS AND METHODS: SPIO nanoparticles functionalized with doxorubicin were synthesized. N1-S1 hepatomas were successfully induced in 17 Sprague-Dawley rats distributed into three dosage groups. Baseline tumor R2* values (the reciprocal of T2*) were determined using 7-tesla (T) MR imaging. After intravenous injection of SPIO nanoparticles, reversible electroporation (1,300 V/cm, 8 pulses, 100-µs pulse duration) was applied. Imaging of rats was performed to determine tumor R2* values after the procedure, and change in R2* (ΔR2*) was calculated. Inductively coupled plasma mass spectrometry was used to determine intratumoral iron (Fe) concentration after the procedure, which served as a proxy for SPIO nanoparticle uptake. Mean tumor Fe concentration [Fe] and ΔR2* for each subject were assessed for correlation with linear regression, and mean [Fe] for each dosage group was compared with analysis of variance. RESULTS: ΔR2* significantly correlated with tumor SPIO nanoparticle uptake after nanoablation (r = 0.50, P = .039). On average, each 0.1-ms(-1) increase in R2* corresponded to a 0.1394-mM increase in [Fe]. There was no significant difference in mean SPIO nanoparticle uptake among dosage groups (P = .57). CONCLUSIONS: Intratumoral SPIO nanoparticle uptake after nanoablation can be successfully quantified noninvasively with 7-T MR imaging. Imaging can be used as a method to estimate localized drug delivery after nanoablation.

Diffusion abnormalities of the corpus callosum in patients receiving bevacizumab for malignant brain tumors: suspected treatment toxicity.

Bevacizumab has been reported to cause diffusion restriction in the tumor bed of patients with malignant gliomas. This study evaluated prolonged diffusion restriction, in the corpus callosum (CC), of patients with malignant brain tumors treated with bevacizumab. We retrospectively reviewed our database of patients treated with bevacizumab for malignant brain tumors looking for those with restricted diffusion in the CC. CC ADC ratio measurements were obtained prior to and following treatment. Correlation was made with biopsy (n = 3) and MR perfusion (n = 7) and PET (n = 4). The temporal evolution of these changes relative to therapy was examined with mixed effects regression analysis. Nine patients (eight malignant gliomas, one malignant meningioma) out of 146 patients were found to have developed areas of diffusion restriction in the CC. These areas tended to enlarge and coalesce over serial MRIs and persisted for up to 22 months. Hypoperfusion was demonstrated in MR perfusion in 7/7. PET was hypometabolic in all 4. Biopsy of the CC showed no tumor in 3/3. ADC ratio measurements indicated a significant overall effect of time (F(16,60) = 11.2; p < 0.0001), consistent with persistent diffusion restriction over the measured time periods. Bevacizumab causes prolonged diffusion restriction in the CC. The negative MR perfusion, FDG PET and histopathology suggest this is a toxicity of bevacizumab and not active tumor. Awareness of these changes can assist in patient care.

Seven-tesla magnetic resonance imaging accurately quantifies intratumoral uptake of therapeutic nanoparticles in the McA rat model of hepatocellular carcinoma: preclinical study in a rodent model.

OBJECTIVES: After inducing McA tumors in Sprague-Dawley rats (McA-SD), the following hypotheses were tested: first, that hypervascular McA tumors grown in Sprague-Dawley rats provide a suitable platform to investigate drug delivery; and second, that high-field MRI can be used to measure intratumoral uptake of DOX-SPIOs. MATERIALS AND METHODS: McA cells were implanted into the livers of 18 Sprague-Dawley rats. In successfully inoculated animals, 220-µL DOX-SPIOs were delivered to tumors via the intravenous or intra-arterial route. Pretreatment and posttreatment T2*-weighted images were obtained using 7-T MRI, and change in R2* value (ΔR2*) was obtained from mean signal intensities of tumors in these images. Tumor iron concentration ([Fe]), an indicator of DOX-SPIO uptake, was measured using mass spectroscopy. The primary outcome variable was the Pearson correlation between ΔR2* and [Fe]. RESULTS: Tumors grew successfully in 13 of the 18 animals (72%). Mean (SD) maximum tumor diameter was 0.83 (0.25) cm. The results of phantom studies revealed a strong positive correlation between ΔR2* and [Fe], with r = 0.98 (P < 0.01). The results of in vivo drug uptake studies demonstrated a positive correlation between ΔR2* and [Fe], with r = 0.72 (P = 0.0004). CONCLUSIONS: The McA tumors grown in the Sprague-Dawley rats demonstrated uptake of nanoparticle-based therapeutic agents. Magnetic resonance imaging quantification of intratumoral uptake strongly correlated with iron concentrations in pathological specimens, suggesting that MRI may be used to quantify uptake of iron-oxide nanotherapeutics.

DuSK: A Dual Structure-preserving Kernel for Supervised Tensor Learning with Applications to Neuroimages.

With advances in data collection technologies, tensor data is assuming increasing prominence in many applications and the problem of supervised tensor learning has emerged as a topic of critical significance in the data mining and machine learning community. Conventional methods for supervised tensor learning mainly focus on learning kernels by flattening the tensor into vectors or matrices, however structural information within the tensors will be lost. In this paper, we introduce a new scheme to design structure-preserving kernels for supervised tensor learning. Specifically, we demonstrate how to leverage the naturally available structure within the tensorial representation to encode prior knowledge in the kernel. We proposed a tensor kernel that can preserve tensor structures based upon dual-tensorial mapping. The dual-tensorial mapping function can map each tensor instance in the input space to another tensor in the feature space while preserving the tensorial structure. Theoretically, our approach is an extension of the conventional kernels in the vector space to tensor space. We applied our novel kernel in conjunction with SVM to real-world tensor classification problems including brain fMRI classification for three different diseases (i.e., Alzheimer's disease, ADHD and brain damage by HIV). Extensive empirical studies demonstrate that our proposed approach can effectively boost tensor classification performances, particularly with small sample sizes.

Tensor-based Multi-view Feature Selection with Applications to Brain Diseases.

In the era of big data, we can easily access information from multiple views which may be obtained from different sources or feature subsets. Generally, different views provide complementary information for learning tasks. Thus, multi-view learning can facilitate the learning process and is prevalent in a wide range of application domains. For example, in medical science, measurements from a series of medical examinations are documented for each subject, including clinical, imaging, immunologic, serologic and cognitive measures which are obtained from multiple sources. Specifically, for brain diagnosis, we can have different quantitative analysis which can be seen as different feature subsets of a subject. It is desirable to combine all these features in an effective way for disease diagnosis. However, some measurements from less relevant medical examinations can introduce irrelevant information which can even be exaggerated after view combinations. Feature selection should therefore be incorporated in the process of multi-view learning. In this paper, we explore tensor product to bring different views together in a joint space, and present a dual method of tensor-based multi-view feature selection (dual-Tmfs) based on the idea of support vector machine recursive feature elimination. Experiments conducted on datasets derived from neurological disorder demonstrate the features selected by our proposed method yield better classification performance and are relevant to disease diagnosis.

Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status.

Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection.

Discriminative Feature Selection for Uncertain Graph Classification.

Mining discriminative features for graph data has attracted much attention in recent years due to its important role in constructing graph classifiers, generating graph indices, etc. Most measurement of interestingness of discriminative subgraph features are defined on certain graphs, where the structure of graph objects are certain, and the binary edges within each graph represent the "presence" of linkages among the nodes. In many real-world applications, however, the linkage structure of the graphs is inherently uncertain. Therefore, existing measurements of interestingness based upon certain graphs are unable to capture the structural uncertainty in these applications effectively. In this paper, we study the problem of discriminative subgraph feature selection from uncertain graphs. This problem is challenging and different from conventional subgraph mining problems because both the structure of the graph objects and the discrimination score of each subgraph feature are uncertain. To address these challenges, we propose a novel discriminative subgraph feature selection method, Dug, which can find discriminative subgraph features in uncertain graphs based upon different statistical measures including expectation, median, mode and φ-probability. We first compute the probability distribution of the discrimination scores for each subgraph feature based on dynamic programming. Then a branch-and-bound algorithm is proposed to search for discriminative subgraphs efficiently. Extensive experiments on various neuroimaging applications (i.e., Alzheimers Disease, ADHD and HIV) have been performed to analyze the gain in performance by taking into account structural uncertainties in identifying discriminative subgraph features for graph classification.

Hippocampal magnetization transfer ratio at 3T: validation of automated postprocessing and comparison of quantification metrics.

BACKGROUND: To investigate the reliability of a novel magnetization transfer ratio (MTR) postprocessing technique for the hippocampus using histogram analysis, and compare results to more established volumetric measurements. This study is conducted in healthy volunteers as a precursor to future applications regarding progressive neurologic diseases, such as Alzheimer's disease. METHODS: Eight healthy subjects were scanned twice with interval of 1 week using quantitative magnetic resonance imaging (MRI). Automated pixel-wise analysis was performed for the hippocampal regions of each patient. Reliability was assessed using intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and instrumental standard deviation (ISD). RESULTS: Reliable metrics were 25th percentile, median, 75th percentile, peak location, and mean approach (ranges: ICC = .93-.96, COV = 2.71-3.88%, ISD .78-1.01). Histogram peak height had ICC below .7, and a COV above 10%. Volumetric measurements had (ICC = .95-.97, COV = 1.43-3.39%). CONCLUSION: Excellent scan-rescan reproducibility (ICC > .9, COV < 10%) was observed for specific MTR histogram metrics and the mean MTR approach. These results are comparable to the volumetric approach. Future studies can examine the possibility that MTR changes precede morphological changes as this study suggests that both MTR and volumetric measurements of the hippocampus can be used as reliable imaging tools.

Structural brain alterations can be detected early in HIV infection.

OBJECTIVE: Brain changes occurring early in HIV infection are not well characterized. The Chicago Early HIV Infection Study aimed to evaluate the presence and extent of structural brain alterations using quantitative MRI. METHODS: Forty-three HIV and 21 control subjects were enrolled. Mean length of infection was estimated as less than 1 year based on assay results. High-resolution neuroanatomical images were acquired. Automated image analysis was used to derive measurements for total brain, ventricular volume, and for tissue classes (total and cortical gray matter, white matter, and CSF). A separate image analysis algorithm was used to calculate measurements for individual brain regions. Cognitive function was assessed by neuropsychological evaluation. RESULTS: Reductions were quantified in total (p = 0.0547) and cortical (p = 0.0109) gray matter in the HIV group. Analysis of individual brain regions with a separate image analysis algorithm revealed consistent findings of reductions in cerebral cortex (p = 0.042) and expansion of third ventricle (p = 0.046). The early HIV group also demonstrated weaker performance on several neuropsychological tests, with the most pronounced difference in psychomotor speed (p = 0.001). CONCLUSIONS: This cross-sectional brain volumetric study indicates structural alterations early in HIV infection. The findings challenge the prevailing assumption that the brain is spared in this period. Revisiting the question of the brain's vulnerability to processes unfolding in the initial virus-host interaction and the early natural history may yield new insights into neurologic injury in HIV infection and inform neuroprotection strategies.