Publications

PURPOSE

To evaluate the feasibility of using contrast material-enhanced computed tomographic (CT) measurements of hepatic fractional extracellular space (fECS) and macromolecular contrast material (MMCM) uptake to measure severity of liver fibrosis.

MATERIALS AND METHODS

All procedures were approved by and executed in accordance with University of California, San Francisco, institutional animal care and use committee regulations. Twenty-one rats that received intragastric CCl(4) for 0-12 weeks were imaged with respiratory-gated micro-CT by using both a conventional contrast material and a novel iodinated MMCM. Histopathologic hepatic fibrosis was graded qualitatively by using the Ishak fibrosis score and quantitatively by using morphometry of the fibrosis area. Hepatic fECS and MMCM uptake were calculated for each examination and correlated with histopathologic findings by using uni- and multivariate linear regressions.

RESULTS

Ishak fibrosis scores ranged from a baseline of 0 in untreated animals to a maximum of 5. Histopathologic liver fibrosis area increased from 0.46% to 3.5% over the same interval. Strong correlations were seen between conventional contrast-enhanced CT measurements of fECS and both the Ishak fibrosis scores (R(2) = 0.751, P < .001) and the fibrosis area (R(2) = 0.801, P < .001). Strong negative correlations were observed between uptake of MMCM in the liver and Ishak fibrosis scores (R(2) = 0.827, P < .001), as well as between uptake of MMCM in the liver and fibrosis area (R(2) = 0.643, P = .001). Multivariate linear regression analysis showed a trend toward independence for fECS and MMCM uptake in the prediction of Ishak fibrosis scores, with an R(2) value of 0.86 (P = .081 and P = .033, respectively).

CONCLUSION

Contrast-enhanced CT measurements of fECS and MMCM uptake are individually capable of being used to estimate the degree of early hepatic fibrosis in a rat model.

SUPPLEMENTAL MATERIAL

http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112452/-/DC1.

BACKGROUND

Left bundle branch block (LBBB) has been proposed as a risk factor for cardiovascular morbidity and mortality. We sought to characterize the strength of these associations in a population without preexisting clinical heart disease.

METHODS

The association between LBBB and new-onset congestive heart failure (CHF) or death from cardiovascular diseases was examined in 1,688 participants enrolled in the SPPARCS study who were free of known CHF or previous myocardial infarction. SPPARCS is a community-based cohort study in residents of Sonoma, California that are > 55 years. Medical history and 12-lead ECGs were obtained every 2 years for up to 6 years of follow-up. LBBB at enrollment or year 2 was considered "baseline" and assessed as a predictor of CHF and cardiovascular death ascertained at years 4 and 6.

RESULTS

The prevalence of LBBB at baseline was 2.5% (n = 42). During 6 years of follow-up, 70 (4.8%) people developed new CHF. Incidence of CHF was higher in patients with LBBB than in participants without LBBB. This association persisted after controlling for potential confounders (odds ratio (OR): 2.85; 95% confidence interval (CI): 1.01 - 8.02; P = 0.047). A higher mortality from cardiovascular diseases was also found in participants with LBBB after adjusting for potential confounders (OR: 2.35, 95%CI: 1.02 - 5.41; P = 0.044).

CONCLUSIONS

LBBB in the absence of a clinically detectable heart disease is associated with new-onset CHF and death from cardiovascular diseases. Further study is warranted to determine if additional diagnostic testing or earlier treatment in patients with asymptomatic LBBB can decrease cardiovascular morbidity or mortality.

BACKGROUND

With improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure.

METHODS

We performed a retrospective cohort analysis using electronic medical records from HIV-infected children who initiated ART at McCord Hospital's Sinikithemba Clinic in KwaZulu-Natal, South Africa, from August 2003 to December 2010. We analyzed all records from children who began second-line ART due to first-line treatment failure. We used logistic regression to compare viral outcomes in Protease Inhibitor (PI)-based versus Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based second-line ART, controlling for time on first-line ART, sex, and whether HIV genotyping guided the regimen change.

RESULTS

Of the 880 children who initiated ART during this time period, 80 (9.1%) switched to second-line ART due to therapeutic failure of first-line ART after a median of 95 weeks (IQR 65-147 weeks). Eight (10%) of the failures received NNRTI-based second-line ART, all of whom failed a PI-based first-line regimen. Seventy (87.5%) received PI-based second-line ART, all of whom failed a NNRTI-based first-line regimen. Two children (2.5%) received non-standard dual therapy as second-line ART. Six months after switching ART regimens, the viral suppression rate was significantly higher in the PI group (82%) than in the NNRTI group (29%; p=0.003). Forty-one children (51%) were tested for genotypic resistance prior to switching to second-line ART. There was no significant difference in six month viral suppression (p=0.38) between children with and without genotype testing.

CONCLUSION

NNRTI-based second-line ART carries a high risk of virologic failure compared to PI-based second-line ART.

In vivo real-time epifluorescence imaging of mouse hind limb vasculatures in the second near-infrared region (NIR-II) is performed using single-walled carbon nanotubes as fluorophores. Both high spatial (∼30 μm) and temporal (<200 ms per frame) resolution for small-vessel imaging are achieved at 1-3 mm deep in the hind limb owing to the beneficial NIR-II optical window that affords deep anatomical penetration and low scattering. This spatial resolution is unattainable by traditional NIR imaging (NIR-I) or microscopic computed tomography, and the temporal resolution far exceeds scanning microscopic imaging techniques. Arterial and venous vessels are unambiguously differentiated using a dynamic contrast-enhanced NIR-II imaging technique on the basis of their distinct hemodynamics. Further, the deep tissue penetration and high spatial and temporal resolution of NIR-II imaging allow for precise quantifications of blood velocity in both normal and ischemic femoral arteries, which are beyond the capabilities of ultrasonography at lower blood velocities.