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Background Matrix metalloproteinases (MMPs) are known to modulate left ventricular (LV) remodeling after a myocardial infarction (MI). However, the temporal and spatial variation of MMP activation and their relationship to mechanical dysfunction post MI remains undefined. Methods and Results MI was surgically induced in pigs (n=23) and cine MR and dual isotope hybrid SPECT/CT imaging obtained using thallium-201 (201Tl) and a technetium-99m labeled MMP targeted tracer (99mTc-RP805) at 1, 2 and 4 weeks post MI along with controls (n=5). Regional myocardial strain was computed from MR images and related to MMP zymography and ex vivo myocardial 99mTc-RP805 retention. MMP activation as assessed by in vivo and ex vivo 99mTc-RP805 imaging/retention studies was increased nearly 5-fold within the infarct region at 1 week post-MI and remained elevated up to 1 month post-MI. The post-MI change in LV end-diastolic volumes was correlated with MMP activity (y=31.34e0.48x, p=0.04). MMP activity was increased within the border and remote regions early post-MI, but declined over 1 month. There was a high concordance between regional 99mTc-RP805 uptake and ex vivo MMP-2 activity. Conclusions A novel, multimodality non-invasive hybrid SPECT/CT imaging approach was validated and applied for in vivo evaluation of MMP activation in combination with cine MR analysis of LV deformation. Increased 99mTc-RP805 retention was seen throughout the heart early post-MI and was not purely a reciprocal of 201Tl perfusion. 99mTc-RP805 SPECT/CT imaging may provide unique information regarding regional myocardial MMP activation and predict late post-MI LV remodeling.

Background Disturbances in sleep associated with chronic cocaine use may underlie abstinence-related cognitive dysfunction. We hypothesized that sleep-related cognitive function would be impaired in chronic cocaine users, and that this impairment would be associated with abstinence-related changes in sleep architecture. Methods Twelve chronic cocaine users completed a 23-day in-patient study that included randomized, placebo-controlled, cocaine self-administration sessions. We report polysomnographic measurement of rapid eye-movement (REM) sleep and slow-wave activity, and performance on a visual texture discrimination task. Findings Progressive abstinence from cocaine was associated with characteristic changes in REM sleep. REM sleep was shortest on nights following cocaine use and rebounded in the first week of abstinence before diminishing with progressive abstinence, following a pattern opposite that of slow-wave activity. Overnight visual learning was observed over the first night following 3 consecutive days of laboratory cocaine use; however, learning was not observed at 3 days or 17 days of abstinence. Across all points of abstinence, early-night slow-wave activity was associated strongly with non-deterioration of visual performance overnight. Furthermore, overnight enhancement of visual performance was predicted by the co-occurrence of sufficient early-night slow-wave activity and late night REM sleep, similar to results from studies in healthy subjects. Conclusions These results suggest that abstinence-associated sleep-dependent learning deficits are related to characteristic changes in sleep architecture, and promote the idea that treatments directed at sleep (`somno-tropic' treatments) could be helpful in offsetting physiological consequences of cocaine abstinence.

Accurate and reproducible SPECT quantification of myocardial molecular processes remains a challenge because of the complication of heterogeneous background and extracardiac activity adjacent to the heart, which causes errors in the estimation of myocardial focal tracer uptake. Our aim in this study was to introduce a heuristic method for the correction of extracardiac activity into SPECT quantification and validate the modified quantification method for accuracy and reproducibility using a canine model. Methods Dual-isotope–targeted 99mTc and 201Tl perfusion SPECT images were acquired using a hybrid SPECT/CT camera in 6 dogs at 2 wk after myocardial infarction. Images were reconstructed with and without CT-based attenuation correction, and the reconstructed SPECT images were filtered and quantified simultaneously with incorporation of extracardiac radioactivity correction, gaussian fitting, and total-count sampling. Absolute myocardial focal tracer uptake was quantified from SPECT images using 3 different normal limits (maximum entropy [ME], mean-squared-error minimization [MSEM], and global minimum [GM]). SPECT-quantified percentage injected dose (%ID) was calculated and compared with the well-counted radioactivity measured from the postmortem myocardial tissue. SPECT quantitative processing was performed by 2 different individuals with extensive experience in cardiac image processing, to assess reproducibility of the quantitative analysis. Results Correlations between SPECT-quantified and well-counted %IDs using 3 different normal limits were excellent (ME: r = 0.82, y = 0.932x − 0.0102; MSEM: r = 0.73, y = 1.1413x − 0.0052; and GM: r = 0.7, y = 1.2147x − 0.0002). SPECT quantification using ME normal limits resulted in an underestimation of %ID, as compared with well-counted %ID. Myocardial focal tracer uptake quantified from SPECT images without CT-based attenuation correction was significantly lower than that with the attenuation correction. The %IDs quantified from attenuation-corrected SPECT images using MSEM and GM normal limits were not significantly different from well-counted %IDs. Reproducibility of the SPECT quantitative analysis was excellent (ME: r = 0.98, y = 0.9221x + 0.0001; MSEM: r = 0.97, y = 0.9357x + 0.0004; and GM: r = 0.96, y = 0.9026x + 0.001). Conclusion Our SPECT/CT quantification algorithm for the assessment of regional radioactivity may allow for accurate and reproducible serial noninvasive evaluation of molecularly targeted tracers in the myocardium.