Detection of Acute Chest Syndrome by MRI in a Sickle Transgenic Mouse Model.

Acute chest syndrome (ACS) is a potentially deadly complication in sickle cell patients, particularly in young adults. In patients younger than 17 years, ACS is frequently associated with infection; however, in adults, association with vasocclusive crisis and fat and bone marrow embolism is more common. We have developed a sickle transgenic mouse model for ACS that consists of injecting a mixture of bone marrow and mouse fat into the tail vein of a sickle transgenic mouse. The mouse used was a NY1 partial KO that expresses 100% human α and 55% β^S. Mice were injected with bone marrow (BM) from two femurs (about 15 mg) and, as murine BM lacks fat, purified peritoneal fat (about 15 mg). Creatine kinase (CK), predominantly the MM form, and sVCAM increased above baseline levels at 6, 24, and 48 hours in NY1 partial KO mice, but not in control C57Bl mice. Magnetic resonance imaging (MRI) was performed at 48 hours after the initial injection. It is normally difficult to perform MR imaging of lung due to its inherently short transverse relaxation time and relatively low proton density relative to other tissue. However, these difficulties can be overcome through the use of ultra short echo time spin echo sequences at high field strength. Spin echo images were obtained using a respiratory-gated spin echo sequences at TE=3 msec and at TE=10 msec. From this data one can calculate a quantitative relaxation rate (1/T2) map and an average value of R2. Decreased values for mean R2 are an indication of fluid accumulation. In NY1 partial KO mice examined 48 hours after injection, the 1/T2 map revealed focal patches with high water content and a mean R2 of 131 vs R2 = 220 for an uninjected control mouse; when the same animals were examined three months later R2s were found to be 181 and 124. C57Bl control mice were also examined at 48 hours post injection, and R2 values of 211 and 178 were found. Pulmonary edema is a defining finding in ACS and its presence in sickle mice, but not in control mice is strong support for this model. The mice survived both the fat/BM injection and the MRI, indicating that it will be possible to obtain repeated images from the same animal to study the natural course of lung injury and interventions that may ameliorate injury.