PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.

Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.

Feasibility of coronary artery wall thickening assessment in asymptomatic coronary artery disease using phase-sensitive dual-inversion recovery MRI at 3T.

OBJECTIVES: The purpose of this study was to (a) investigate the image quality of phase-sensitive dual-inversion recovery (PS-DIR) coronary wall imaging in healthy subjects and in subjects with known coronary artery disease (CAD) and to (b) investigate the utilization of PS-DIR at 3T in the assessment of coronary artery thickening in subjects with asymptomatic but variable degrees of CAD. MATERIALS AND METHODS: A total of 37 subjects participated in this institutional review board-approved and HIPAA-compliant study. These included 21 subjects with known CAD as identified on multidetector computed tomography angiography (MDCT). Sixteen healthy subjects without known history of CAD were included. All subjects were scanned using free-breathing PS-DIR magnetic resonance imaging (MRI) for the assessment of coronary wall thickness at 3T. Lumen-tissue contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR) and quantitative vessel parameters including lumen area and wall thickness were measured. Statistical analyses were performed. RESULTS: PS-DIR was successfully completed in 76% of patients and in 88% of the healthy subjects. Phase-sensitive signed-magnitude reconstruction, compared to modulus-magnitude images, significantly improved lumen-tissue CNR in healthy subjects (26.73±11.95 vs. 14.65±9.57, P<.001) and in patients (21.45±7.61 vs. 16.65±5.85, P<.001). There was no difference in image CNR and SNR between groups. In arterial segments free of plaques, coronary wall was thicker in patients in comparison to healthy subjects (1.74±0.27 mm vs. 1.17±0.14 mm, P<.001), without a change in lumen area (4.51±2.42 mm2 vs. 5.71±3.11mm2, P=.25). CONCLUSIONS: This is the first study to demonstrate the feasibility of successfully obtaining vessel wall images at 3T using PS-DIR in asymptomatic patients with known variable degrees of CAD as detected by MDCT. This was achieved with a fixed subject-invariant planning of blood signal nulling. With that limitation alleviated, PS-DIR coronary wall MRI is capable of detecting arterial thickening and positive arterial remodeling at 3T in asymptomatic CAD.