Objectives

The aim of this work is the development of coronary atherosclerosis T₁-weighted characterization with integrated anatomical reference (CATCH) technique and the validation by comparison with high-risk plaque features (HRPF) observed on intracoronary optical coherence tomography (OCT) and invasive coronary angiography.

Background

T₁-weighted cardiac magnetic resonance with or without contrast media has been used for characterizing coronary atherosclerosis showing promising prognostic value. Several limitations include: 1) coverage is limited to proximal coronary segments; 2) spatial resolution is low and often anisotropic; and 3) a separate magnetic resonance angiography acquisition is needed to localize lesions.

Methods

CATCH acquired dark-blood T₁-weighted images and bright-blood anatomical reference images in an interleaved fashion. Retrospective motion correction with 100% respiratory gating efficiency was achieved. Reference control subjects (n = 13) completed both pre- and post-contrast scans. Stable angina patients (n = 30) completed pre-contrast scans, among whom 26 eligible patients also completed post-contrast scans. After cardiac magnetic resonance, eligible patients (n = 22) underwent invasive coronary angiography and OCT for the interrogation of coronary atherosclerosis. OCT images were assessed and scored for HRPF (lipid-richness, macrophages, cholesterol crystals, and microvessels) by 2 experienced analysts blinded to magnetic resonance results.

Results

Per-subject analysis showed none of the 13 reference control subjects had coronary hyperintensive plaques (CHIP) in either pre-contrast or post-contrast CATCH. Five patients had CHIP on pre-contrast CATCH and 5 patients had CHIP on post-contrast CATCH. Patients with CHIP had greater lipid abnormality than those without. Per-segment analysis showed elevated pre- and post-contrast plaque to myocardium signal ratio in the lesions with HRPF versus those without. Positive correlation was observed between plaque to myocardium signal ratio and OCT HRPF scoring. CHIP on pre-contrast CATCH were associated with significantly higher stenosis level than non-CHIP on invasive coronary angiography.

Conclusions

CATCH provided accelerated whole heart coronary plaque characterization with simultaneously acquired anatomical reference. CHIP detected by CATCH showed positive association with high-risk plaque features on invasive imaging studies.

Purpose

To investigate the feasibility of blood pressure difference measurement, ΔP, across the coronary artery using phase contrast (PC)-MRI for potential noninvasive assessment of the functional significance of coronary artery stenosis.

Methods

Three-directional velocities in the coronary arteries acquired using 2D-PC-MRI were used with the Navier-Stokes equations to derive ΔP. Repeat phantom studies were performed to assess the reproducibility of flow velocity and ΔP. ΔP derived using PC-MRI (ΔP_MR ) and that obtained using pressure transducer (ΔP_PT ) were compared. Reproducibility of coronary flow velocity was assessed in healthy controls (n = 11). Patients with suspected coronary artery disease (n = 6) were studied to evaluate the feasibility of ΔP_MR measurement across a coronary stenosis.

Results

Phantom: Good overall reproducibility of flow velocity and ΔP measurements and excellent correlation (ΔP_MR vs ΔP_PT ) was observed: intraclass correlation (ICC) of 0.95(V_z ), 0.72(V_x ), 0.73(V_y ), and 0.87(ΔP_MR ) and R²  = 0.94, respectively. Human: Good reproducibility of coronary flow velocity was observed: ICC of 0.94/0.95(V_z ), 0.76/0.74(V_x ), and 0.80/0.77(V_y ) at cardiac phase 1/2. Significant (p = 0.025) increase in ΔP_MR was observed in patients (6.40 ± 4.43 mmHg) versus controls (0.70 ± 0.57 mmHg).

Conclusion

ΔP_MR in the coronary arteries is feasible. Upon further validation using the invasive measure, ΔP_MR has the potential for noninvasive assessment of coronary artery stenosis. Magn Reson Med 77:529-537, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Background

HIV-associated neurocognitive disorders (HANDs) afflict more than half of HIV-1-positive individuals. The transactivator of transcription (Tat) produced by HIV virus elicits inflammatory process and is a major neurotoxic mediator that induce neuron damage during HAND pathogenesis. Activated astrocytes are important cells involved in neuroinflammation and neuronal damage. Purinergic receptors expressed in astrocytes participate in a positive feedback loop in virus-induced neurotoxicity. Here, we investigated that whether P2Y4R, a P2Y receptor subtype, that expressed in astrocyte participates in Tat-induced neuronal death in vitro and in vivo.

Methods

Soluble Tat protein was performed to determine the expression of P2Y4R and proinflammatory cytokines in astrocytes using siRNA technique via real-time PCR, Western blot, and immunofluorescence assays. Cytometric bead array was used to measure proinflammatory cytokine release. The TUNEL staining and MTT cell viability assay were analyzed for HT22 cell apoptosis and viability, and the ApopTag® peroxidase in situ apoptosis detection kit and cresyl violet staining for apoptosis and death of hippocampal neuron in vivo.

Results

We found that Tat challenge increased the expression of P2Y4R in astrocytes. P2Y4R signaling in astrocytes was involved in Tat-induced inflammatory cytokine production via PI3K/Akt- and ERK1/2-dependent pathways. Knockdown of P2Y4R expression significantly reduced inflammatory cytokine production and relieved Tat-mediated neuronal apoptosis in vitro. Furthermore, in vivo challenged with Tat, P2Y4R knockdown mice showed decreased inflammation and neuronal damage, especially in hippocampal CA1 region.

Conclusions

Our data provide novel insights into astrocyte-mediated neuron damage during HIV-1 infection and suggest a potential therapeutic target for HANDs.