The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, we demonstrate that a transactivator of transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with a 5 nm core size is capable of crossing the BBB efficiently and delivering cargoes such as the anticancer drug doxorubicin (Dox) and Gd3+ contrast agents to brain tumor tissues. Treatment of mice bearing intracranial glioma xenografts with pH-sensitive Dox-conjugated TAT-Au NPs via a single intravenous administration leads to significant survival benefit when compared to the free Dox. Furthermore, we demonstrate that TAT-Au NPs are capable of delivering Gd3+ chelates for enhanced brain tumor imaging with a prolonged retention time of Gd3+ when compared to the free Gd3+ chelates. Collectively, these results show promising applications of the TAT-Au NPs for enhanced malignant brain tumor therapy and non-invasive imaging.
Purpose: To determine relative diagnostic value of MR diffusion and perfusion parameters in detection of active small bowel inflammation in patients with Crohn's disease (CD).
Materials and Methods:We reviewed 18 patients with active CD of terminal ileum (TI) who underwent MR enterography (MRE; including dynamic contrast enhanced MRI and diffusion-weighted MRI). Conventional MRI findings of TI were recorded. Regions of interest were drawn over TI and normal ileum to calculate apparent diffusion coefficient (ADC), the volume transfer constant (K trans ) and the contrast media distribution volume (v e ). Receiver operating characteristic analysis was used to determine their diagnostic performance.Results: Among conventional MR findings, mural thickening and increased enhancement were present in all actively inflamed small bowel. K Conclusion: Dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) provide quantitative measures of small bowel inflammation that can differentiate actively inflamed small bowel segments from normal small bowel in CD. DWI provides better sensitivity compared with DCE-MRI and combination of ADC and K trans parameters for analysis can potentially improve specificity.
HB1.F3.CD NSCs loaded with CRAd-Survivin-pk7 overcome major limitations of OV in vivo and warrant translation in a phase I human clinical trial for patients with GBM.
Dynamic contrast-enhanced MRI (DCEMRI) data were acquired from metastatic and nonmetastatic tumors in rodents to follow the uptake and washout of a low-molecular-weight contrast agent (Gd-DTPA) and a contrast agent with higher molecular weight (P792). The concentration vs. time curves calculated for the tumor rims and centers were analyzed using the two-compartment model (TCM) and a newly developed empirical mathematical model (EMM). The EMM provided improved fits to the experimental data compared to the TCM. Parameters derived from the empirical model showed that the contrast agent washout rate was significantly slower in metastatic tumors than in nonmetastatic tumors for both Gd-DTPA (P < 0.03) and P792 (P < 0.04). The effects of the tumor on blood flow in "normal" tissue immediately adjacent to the tumors were evident: Gd-DTPA uptake and washout rates were much lower in muscle near the tumor (P < 0.05) than normal muscle farther from the tumor. The results suggest that accurate fits of DCEMRI data provide kinetic parameters that distinguish between metastatic and relatively benign cancers. In addition, a comparison of the dynamics of Gd-DTPA and P792 provides information regarding the microenvironment of tumors.
Repetitive transcranial magnetic stimulation is a beneficial neurorehabilitative strategy for enhancing motor recovery in the acute and subacute phase after stroke.
Perfluorocarbon (PFC) emulsions can be imaged directly by fluorine-19 MRI. We developed an optimized protocol for preparing PFC droplets of uniform size, evaluated use of the resulting droplets as blood pool contrast agents, studied their uptake by tumours and determined the spatial resolution with which they can be imaged at 4.7 T. Perfluorocarbon droplets of three different average sizes (324, 293 and 225 nm) were prepared using a microemulsifier. Images of PFC droplets with good signal-to-noise ratio were acquired with 625 microm in-plane resolution, 3 mm slice thickness and acquisition time of approximately 4.5 min per image. Kinetics of washout were determined using a simple mathematical model. The maximum uptake of the PFC droplets was three times greater at the tumour rim than in muscle, but the washout rate was two to three times slower in the tumour. The results are consistent with leakage of the droplets into the tumour extravascular space due to the hyper-permeability of tumour capillaries. PFC droplets may allow practical and quantitative measurements of blood volume and capillary permeability in tumours with reasonable spatial resolution.
Rationale and objectives
To evaluate the feasibility and advantages of a combined high temporal/high spatial resolution protocol for DCE-MRI of the breast.
Materials and methods
Twenty-three patients with enhancing lesions were imaged at 3T. The acquisition protocol consisted of a series of bilateral, fat-suppressed ‘ultrafast’ acquisitions, with 6.9-9.9 s temporal resolution, for the first minute following contrast injection; followed by four high spatial resolution acquisitions with 60–79.5 s temporal resolution. All images were acquired with standard uniform Fourier sampling. A filtering method was developed to reduce noise and detect significant enhancement in the high temporal resolution images. Time-of-arrival (TOA) was defined as the time at which each voxel first satisfied all the filter conditions, relative to the time of initial arterial enhancement.
Results
Ultrafast images improved visualization of the vasculature feeding and draining lesions. A small percentage of the entire field-of-view (<6%) enhanced significantly in the 30 s following contrast injection. Lesion conspicuity was highest in early ultrafast images, especially in cases with marked parenchymal enhancement. While the sample size was relatively small, the average TOA for malignant lesions was significantly shorter than the TOA for benign lesions. Significant differences were also measured in other parameters descriptive of early contrast media uptake kinetics (p<0.05).
Conclusions
Ultrafast imaging in the first minute of breast DCE-MRI has the potential to add valuable information regarding early contrast dynamics. Ultrafast imaging could allow radiologists to confidently identify lesions in the presence of marked background parenchymal enhancement.
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