Publications
Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.
2017
2017
2017
BACKGROUND AND PURPOSE
Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current therapies are associated with high morbidities. Excessive vascular endothelial growth factor has been implicated in bAVM pathophysiology. Because soluble FLT1 binds to vascular endothelial growth factor with high affinity, we tested intravenous delivery of an adeno-associated viral vector serotype-9 expressing soluble FLT1 (AAV9-sFLT1) to alleviate the bAVM phenotype.
METHODS
Two mouse models were used. In model 1, bAVM was induced in R26CreER; mice through global gene deletion and brain focal angiogenic stimulation; AAV2-sFLT02 (an AAV expressing a shorter form of sFLT1) was injected into the brain at the time of model induction, and AAV9-sFLT1, intravenously injected 8 weeks after. In model 2, SM22αCre; mice had a 90% occurrence of spontaneous bAVM at 5 weeks of age and 50% mortality at 6 weeks; AAV9-sFLT1 was intravenously delivered into 4- to 5-week-old mice. Tissue samples were collected 4 weeks after AAV9-sFLT1 delivery.
RESULTS
AAV2-sFLT02 inhibited bAVM formation, and AAV9-sFLT1 reduced abnormal vessels in model 1 (GFP versus sFLT1: 3.66±1.58/200 vessels versus 1.98±1.29, <0.05). AAV9-sFLT1 reduced the occurrence of bAVM (GFP versus sFLT1: 100% versus 36%) and mortality (GFP versus sFLT1: 57% [12/22 mice] versus 24% [4/19 mice], <0.05) in model 2. Kidney and liver function did not change significantly. Minor liver inflammation was found in 56% of AAV9-sFLT1-treated model 1 mice.
CONCLUSIONS
By applying a regulated mechanism to restrict sFLT1 expression to bAVM, AAV9-sFLT1 can potentially be developed into a safer therapy to reduce the bAVM severity.
View on PubMed2017
Katherine Possin and colleagues report on the implementation, development, and early findings of the Care Ecosystem, an adaptive, personalized, and scalable dementia care program.
View on PubMed2017
2017
PURPOSE
To develop a single-shot spiral perfusion pulse sequence with outer-volume suppression (OVS) to achieve whole-heart coverage with a short temporal footprint of 10 ms per slice location.
METHODS
A highly accelerated single-shot variable density spiral pulse sequence with an integrated OVS module for reduced field of view (rFOV) perfusion imaging with 2 mm spatial resolution was developed and evaluated in simulations, phantom experiments and in clinical patients with (n = 8) or without (n = 8) OVS. Images were reconstructed by block low-rank sparsity with motion guidance (BLOSM) and graded by two cardiologists on a 5-point scale (1, excellent; 5, poor).
RESULTS
Simulation and phantom results showed that OVS effectively suppressed the signal outside the desired field of view (FOV). Clinical patient data demonstrated high quality perfusion images with rFOV. The average image quality scores of full FOV cases and rFOV cases were 3.1 ± 0.64 and 2.3 ± 0.46, respectively, (P = 0.02) from cardiologist 1 and 2.5 ± 0.54 and 1.8 ± 0.47, respectively, (P = 0.04) from cardiologist 2, showing superior image quality for the rFOV images compared with the full FOV images.
CONCLUSION
A single-shot spiral perfusion sequence that uses OVS and BLOSM performs perfusion imaging with a very short temporal footprint per image supporting whole-heart coverage with good image quality. Magn Reson Med 79:208-216, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
View on PubMed2017
2017
2017