Publications

BACKGROUND

Macrophages contribute to the progression and acute complications of atherosclerosis. Macrophage imaging may serve as a biomarker to identify subclinical inflamed lesions, to predict future risk, and to aid in the assessment of novel therapies.

METHODS AND RESULTS

To test the hypothesis that nanoparticle-enhanced, high-resolution magnetic resonance imaging (MRI) can measure plaque macrophage accumulation, we used 3-T MRI with a macrophage-targeted superparamagnetic nanoparticle preparation (monocrystalline iron oxide nanoparticles-47 [MION-47]) in cholesterol-fed New Zealand White rabbits 6 months after balloon injury. In vivo MRI visualized thickened abdominal aortas on both T1- and T2-weighted spin-echo images (T1 spin echo, 20 axial slices per animal; T2 spin echo, 28 slices per animal). Seventy-two hours after MION-47 injection, aortas exhibited lower T2 signal intensity compared with before contrast imaging (signal intensity ratio, aortic wall/muscle: before, 1.44 ± 0.26 versus after, 0.95 ± 0.22; 164 slices; P<0.01), whereas T1 spin echo images showed no significant change. MRI on ex vivo specimens provided similar results. Histological studies colocalized iron accumulation with immunoreactive macrophages in atheromata. The magnitude of signal intensity reduction on T2 spin echo in vivo images further correlated with macrophage areas in situ (150 slices; r=0.73). Treatment with rosuvastatin for 3 months yielded diminished macrophage content (P<0.05) and reversed T2 signal intensity changes (P<0.005). Signal changes in rosuvastatin-treated rabbits correlated with reduced macrophage burden (r=0.73). In vitro validation studies showed concentration-dependent MION-47 uptake by human primary macrophages.

CONCLUSION

The magnitude of T2 signal intensity reduction in high-resolution MRI after administration of superparamagnetic phagocytosable nanoparticles can assess macrophage burden in atheromata, providing a clinically translatable tool to identify inflamed plaques and to monitor therapy-mediated changes in plaque inflammation.

BACKGROUND

It is unclear whether lack of follow-up after screening fecal occult blood testing (FOBT) in older adults is due to screening patients whose comorbidity or preferences do not permit follow-up vs failure to complete follow-up in healthy patients.

METHODS

A prospective cohort study of 2410 patients 70 years or older screened with FOBT was conducted at 4 Veteran Affairs (VA) medical centers from January 1 to December 31, 2001. The main outcome measure was receipt of follow-up within 1 year of FOBT based on national VA and Medicare data. For patients with positive FOBT results, age and Charlson comorbidity scores were evaluated as potential predictors of receiving a complete colon evaluation (colonoscopy or sigmoidoscopy plus barium enema), and medical records were reviewed to determine reasons for lack of follow-up.

RESULTS

A total of 212 patients (9%) had positive FOBT results; 42% received a complete colon evaluation within 1 year. Age and comorbidity were not associated with receipt of a complete follow-up, which was similar among patients 70 to 74 years old with a Charlson score of 0 compared with patients 80 years or older with a Charlson score of 1 or higher (48% vs 41%; P=.28). The VA site, number of positive FOBT cards, and number of VA outpatient visits were predictors. Of 122 patients who did not receive a complete follow-up within 1 year, 38% had documentation that comorbidity or preferences did not permit follow-up, and over the next 5 years 76% never received a complete follow-up.

CONCLUSIONS

While follow-up after positive FOBT results was low regardless of age or comorbidity, screening patients in whom complete evaluation would not be pursued substantially contributes to lack of follow-up. Efforts to improve follow-up should address the full chain of decision making, including decisions to screen and decisions to follow up.