Chronic cocaine administration causes extensive white matter damage in brain: diffusion tensor imaging and immunohistochemistry studies.

The effect of chronic cocaine exposure on multiple white matter structures in rodent brain was examined using diffusion tensor imaging (DTI), locomotor behavior, and end point histology. The animals received either cocaine at a dose of 100mg/kg (N=19), or saline (N=17) for 28 days through an implanted osmotic minipump. The animals underwent serial DTI scans, locomotor assessment, and end point histology for determining the expressions of myelin basic protein (MBP), neurofilament-heavy protein (NF-H), proteolipid protein (PLP), Nogo-A, aquaporin-4 (AQP-4), and growth associated protein-43 (GAP-43). Differences in the DTI measures were observed in the splenium (scc) and genu (gcc) of the corpus callosum (cc), fimbria (fi), and the internal capsule (ic). A significant increase in the activity in the fine motor movements and a significant decrease in the number of rearing events were observed in the cocaine-treated animals. Reduced MBP and Nogo-A and increased GAP-43 expressions were most consistently observed in these structures. A decrease in the NF-H expression was observed in fi and ic. The reduced expression of Nogo-A and the increased expression of GAP-43 may suggest destabilization of axonal connectivity and increased neurite growth with aberrant connections. Increased GAP-43 suggests drug-induced plasticity or a possible repair mechanism response. The findings indicated that multiple white matter tracts are affected following chronic cocaine exposure.

Improved three-dimensional Look-Locker acquisition scheme and angle map filtering procedure for T1 estimation.

The three-dimensional (3D) Look-Locker (LL) acquisition is a widely used fast and efficient T1 mapping method. However, the multi-shot approach of 3D LL acquisition can introduce reconstruction artifacts that result in intensity distortions. Traditional 3D LL acquisition generally utilizes a centric encoding scheme that is limited to a single phase-encoding direction in k space. To optimize k-space segmentation, an elliptical scheme with two phase-encoding directions is implemented for the LL acquisition. This elliptical segmentation can reduce the intensity errors in the reconstructed images and improve the final T1 estimation. One of the major sources of error in LL-based T1 estimation is a lack of accurate knowledge of the actual flip angle. A multi-parameter curve-fitting procedure can account for some of the variability in the flip angle. However, curve fitting can also introduce errors in the estimated flip angle that can result in incorrect T1 values. A filtering procedure based on goodness of fit (GOF) is proposed to reduce the effect of false flip angle estimates. Filtering based on GOF weighting can remove probable incorrect angles that result in bad curve fitting. Simulation, phantom and in vivo studies have demonstrated that these techniques can improve the accuracy of 3D LL T1 estimation.

Validating bladder cancer xenograft bioluminescence with magnetic resonance imaging: the significance of hypoxia and necrosis.

OBJECTIVE: To assess the correlation in orthotopic bladder xenografts of bioluminescence imaging (BLI) with tumour volume as determined by magnetic resonance imaging (MRI), and to define the potential role of hypoxia and necrosis in the relationship between BLI and tumour volume at autopsy. MATERIALS AND METHODS: Orthotopic bladder tumours were established in nude mice with KU7 and 253J B-V cells expressing luciferase. BLI and MRI were performed weekly. Tumour volume was calculated from MR images at each time point. Autopsy was performed 4 weeks after inoculation and 45 min after injection of piminidazole. haematoxylin and eosin staining and immunohistochemical analysis of piminidazole adduct formation were performed on 1-mm step-sections through frozen whole bladder specimens to assess necrosis and hypoxia, respectively. CD31 staining was used to evaluate vascularity. Relative volumes of each specimen containing total tumour, hypoxic tumour and necrotic tumour were quantified. RESULTS: The correlation between MRI volume and BLI was weak in KU7 xenografts (R(2) < 0.1) but strong in 253J B-V (R(2) = 0.93 at 4 weeks). KU7 xenografts had vasculature only peripherally and showed extensive hypoxic and necrotic areas. After subtraction of necrotic areas, the correlation of BLI to viable tumour volume improved (R(2) = 0.42). CONCLUSION: The correlation between tumour BLI and tumour size varies by cell line and is poor in xenografts that rapidly outgrow their vascular supply and develop broad areas of hypoxia and necrosis. However, in these cases BLI does yield information about the amount of viable tumour, and should therefore still be considered as a useful imaging method.

Perfusion in rat brain at 7 T with arterial spin labeling using FAIR-TrueFISP and QUIPSS.

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling is reported. A flow-sensitive alternating recovery sequence, coupled with a balanced gradient fast imaging with steady-state precession readout section was used to minimize ghosting and geometric distortions, while achieving high signal-to-noise ratio. The quantitative imaging of perfusion using a single subtraction method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the imaging slice. Studies in six rats at 7 T showed good perfusion contrast with minimal geometric distortion. The measured blood flow values of 152.5+/-6.3 ml/100 g per minute in gray matter and 72.3+/-14.0 ml/100 g per minute in white matter are in good agreement with previously reported values based on autoradiography, considered to be the gold standard.

Multiple-mouse MRI with multiple arrays of receive coils.

Compared to traditional single-animal imaging methods, multiple-mouse MRI has been shown to dramatically improve imaging throughput and reduce the potentially prohibitive cost for instrument access. To date, up to a single radiofrequency coil has been dedicated to each animal being simultaneously scanned, thus limiting the sensitivity, flexibility, and ultimate throughput. The purpose of this study was to investigate the feasibility of multiple-mouse MRI with a phased-array coil dedicated to each animal. A dual-mouse imaging system, consisting of a pair of two-element phased-array coils, was developed and used to achieve acceleration factors greater than the number of animals scanned at once. By simultaneously scanning two mice with a retrospectively gated cardiac cine MRI sequence, a 3-fold acceleration was achieved with signal-to-noise ratio in the heart that is equivalent to that achieved with an unaccelerated scan using a commercial mouse birdcage coil.

Wireless self-gated multiple-mouse cardiac cine MRI.

Despite the excellent image-contrast capability of MRI and the ability to synchronize MRI with the murine cardiac cycle, this technique is underused for assessing mouse models of cardiovascular disease because of its perceived cost and complexity. This perception stems, in part, from complications associated with the placement and adjustment of electrocardiographic leads that may interact with gradient pulses and the relatively long acquisition times required with traditional gating schemes. To improve the efficiency and reduce the cost and complexity of using cardiac MRI in mice, we combined wireless self-gating techniques (with which we derived cardiac synchronization signals from acquired data) with an imaging technique that acquires multislice cardiac cine images from four mice simultaneously. As a result, the wireless self-gated acquisitions minimized animal preparation time and improved image quality. The simultaneous acquisition of cardiac cine data from multiple animals greatly increased throughput and reduced costs associated with instrument access.

Magnetic resonance imaging of therapy-induced necrosis using gadolinium-chelated polyglutamic acids.

PURPOSE: Necrosis is the most common morphologic alteration found in tumors and surrounding normal tissues after radiation therapy or chemotherapy. Accurate measurement of necrosis may provide an early indication of treatment efficacy or associated toxicity. The purpose of this report is to evaluate the selective accumulation of polymeric paramagnetic magnetic resonance (MR) contrast agents--gadolinium p-aminobenzyl-diethylenetriaminepentaacetic acid-poly(glutamic acid) (L-PG-DTPA-Gd and D-PG-DTPA-Gd)--in necrotic tissue. METHODS AND MATERIALS: Two different solid tumor models, human Colo-205 xenograft and syngeneic murine OCA-1 ovarian tumors, were used in this study. Necrotic response was induced by treatment with poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL). T(1)-weighted spin-echo images were obtained immediately and up to 4 days after contrast injection and compared with corresponding histologic specimens. Two low-molecular-weight contrast agents, DTPA-Gd and oligomeric(L-glutamic acid)-DTPA-Gd, were used as nonspecific controls. RESULTS: Initially, there was minimal tumor enhancement after injection of either L-PG-DTPA-Gd or D-PG-DTPA-Gd, but rapid enhancement after injection of low-molecular-weight agents. However, polymeric contrast agents, but not low-molecular-weight contrast agents, caused sustained enhancement in regions of tumor necrosis in both tumors treated with PG-TXL and untreated tumors. These data indicate that high molecular weight, rather than in vivo biodegradation, is necessary for the specific localization of polymeric MR contrast agents to necrotic tissue. Moreover, biotinylated L-PG-DTPA-Gd colocalized with macrophages in the tumor necrotic areas, suggesting that selective accumulation of L- and D-PG-DTPA-Gd in necrotic tissue was mediated through residing macrophages. CONCLUSIONS: Our data suggest that MR imaging with PG-DTPA-Gd may be a useful technique for noninvasive characterization of treatment-induced necrosis.

Bifunctional Gold Nanoshells with a Superparamagnetic Iron Oxide-Silica Core Suitable for Both MR Imaging and Photothermal Therapy.

We describe the synthesis, characterization, and use of hybrid nanoparticles with a superparamagnetic iron oxide (SPIO) core and a gold nanoshell. These multifunctional nanoparticles, designated SPIO-Au nanoshells, displayed superparamagnetic characteristics and a significant absorbance in the near-infrared (NIR) region of the electromagnetic spectrum. In addition, they exhibited high transverse relaxivity, r2 , and a large r2/r1 ratio and therefore could be imaged by MRI to obtain T2-weighted images. Moreover, SPIO-Au nanoshells showed efficient photo-thermal effect when exposed to NIR light. The use of SPIO-Au nanoshells, with their combination of unique magnetic and optical properties, should enhance the efficacy of nanoshell-mediated photo-thermal therapy by making it possible to direct more nanoparticles to tumors through the application of external magnetic field and by permitting real-time in vivo MRI imaging of the distribution of the nanoparticles before, during, and after photo-thermal therapy.