Biomedical subjects

Erik M Shapiro

Publications and source records attributed to Erik M Shapiro.

13 recordsLinked to original sources

PubMed2006

Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain.

Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in rodents. These NPCs give rise to neural precursors in adults that migrate to the olfactory bulb (OB) along a well-defined pathway, the rostral migratory stream (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats with fluorescent, micron-sized iron oxide particles (MPIOs), and that magnetic resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs along the RMS to the OB. Immunohistochemistry and electron microscopy indicated that particles were inside GFAP(+) neural progenitor cells in the SVZ, migrating PSA-NCAM(+) and Doublecortin(+) neural precursors within the RMS and OB, and Neu-N(+) mature neurons in the OB. This work demonstrates that in vivo cell labeling of progenitor cells for MRI is possible and enables the serial, non-invasive visualization of endogenous progenitor/precursor cell migration.

Animals↗

PubMed2006

In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.

Animals↗

PubMed2005

Sizing it up: cellular MRI using micron-sized iron oxide particles.

There is rapidly increasing interest in the use of MRI to track cell migration in intact animals. Currently, cell labeling is usually accomplished by endocytosis of nanometer-sized, dextran-coated iron oxide particles. The limitations of using nanometer-sized particles, however, are that millions of particles are required to achieve sufficient contrast, the label can be diluted beyond observability by cell division, and the label is biodegradable. These problems make it difficult to label cells other than macrophages in vivo, and to conduct long-term engraftment studies. It was recently demonstrated that micron-sized iron oxide particles (MPIOs) can be taken up by a number of cell types. In this study we examined the MRI properties of single MPIOs with sizes of 0.96, 1.63, 2.79, 4.50, and 5.80 microm. Furthermore, the capacity of cells to endocytose these MPIOs was investigated, and the MRI properties of the labeled cells at 7.0 and 11.7 Tesla were measured as a function of image resolution and echo time (TE). Cells labeled with MPIOs generally contained iron levels of approximately 100 pg, which is approximately threefold higher than those obtained with the best strategies to label cells using nanometer-sized particles. On occasion, some cells had levels as high as approximately 400 pg. We demonstrate that these large particles and the cells labeled with them can be detected by spin echo (SE)-based imaging methods. These measurements indicate that MPIOs should be useful for improving cell tracking by MRI.

Animals↗

PubMed2004

MRI detection of single particles for cellular imaging.

There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 microm indicated that T(2)* effects can be readily detected from single MPIOs at 50-microm resolution and significant signal effects could be detected at resolutions as low as 200 microm. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into single-cell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging.

Animals↗

PubMed2004

Cartilage volume quantification via Live Wire segmentation.

RATIONALE AND OBJECTIVES: A reduction in cartilage volume is characteristic of osteoarthritis and hence there exists a need for an accurate and reproducible method to measure in vivo cartilage volume. Quantification of cartilage volume from magnetic resonance (MR) images requires a segmentation technique such as the user-driven "Live Wire" strategy that can reliably delineate object volumes in a time-efficient manner. In the present work, the accuracy and reproducibility of the Live Wire method for the quantification of cartilage volume in MR images is evaluated. MATERIALS AND METHODS: The accuracy of the Live Wire method was assessed by comparing the MR-based volume measurement of a patellar cartilage-shaped phantom versus data calculated via water displacement. The inter- and intra-operator reproducibility of the technique was evaluated from Live Wire segmentation of the patellar cartilage volume from fat-suppressed 3-dimensional spoiled-gradient-echo images of five healthy human volunteers performed by three operators. To provide data for analysis of inter-scan reproducibility, the human scans were repeated five times with the aid of a leg-restraining jig to minimize repositioning error. RESULTS: The volume of the patellar cartilage-shaped phantom measured via Live Wire segmentation of MR images was within 97.8% of its true volume. The average inter- and intra-operator coefficients of variation of three operators were 3.0% and 0.4%, respectively. The average inter-scan coefficient of variation of five repeated scans of each volunteer was 2.7%. CONCLUSION: The data suggest that the Live Wire strategy is an accurate, reproducible, and efficient technique to measure cartilage volume in vivo in a feasible amount of operator time.

Adult↗

PubMed2004

Proteoglycan loss in human knee cartilage: quantitation with sodium MR imaging--feasibility study.

The feasibility of using sodium magnetic resonance (MR) imaging to detect proteoglycan loss in early-stage osteoarthritis is evaluated. Fixed charge density (FCD) maps were calculated from sodium MR imaging data collected in nine healthy volunteers and three individuals with symptoms of early-stage osteoarthritis by using a 4.0-T clinical MR imaging unit. Data from the healthy individuals revealed a mean FCD of -182 mmol/L +/- 9. Data from the symptomatic subjects revealed focal regions of decreased FCD, with mean values ranging from -108 to -144 mmol/L, indicating proteoglycan loss from the cartilage matrix. The data suggest that sodium MR imaging has potential for use as a quantitative diagnostic tool to measure changes in proteoglycan content in early-stage osteoarthritis.

Adult↗

PubMed2003

Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells.

Tracking transplanted stem cells using magnetic resonance imaging (MRI) could offer biologic insight into homing and engraftment. Ultrasmall dextran-coated iron oxide particles have previously been developed for uptake into cells to allow MRI tracking. We describe a new application of much larger, micron-scale, iron oxide magnetic particles with enhanced MR susceptibility, which enables detection of single cells at resolutions that can be achieved in vivo. In addition, these larger particles possess a fluorophore for histologic confirmation of cell distribution. We demonstrate highly efficient, nontoxic, endosomal uptake of these particles into hematopoietic CD34+ cells and mesenchymal stem cells documented by confocal and electron microscopy. Labeled cells retain biologic activity with preservation of colony-forming ability and differentiation capacity. MRI studies could detect labeled CD34+ cells and mesenchymal stem cells (MSCs) at single cell resolution. This appears to be a promising tool for serial noninvasive monitoring of in vivo cell homing and localization using MRI.

Animals↗

PubMed2003

Three-dimensional T1rho-weighted MRI at 1.5 Tesla.

PURPOSE: To design and implement a magnetic resonance imaging (MRI) pulse sequence capable of performing three-dimensional T(1rho)-weighted MRI on a 1.5-T clinical scanner, and determine the optimal sequence parameters, both theoretically and experimentally, so that the energy deposition by the radiofrequency pulses in the sequence, measured as the specific absorption rate (SAR), does not exceed safety guidelines for imaging human subjects. MATERIALS AND METHODS: A three-pulse cluster was pre-encoded to a three-dimensional gradient-echo imaging sequence to create a three-dimensional, T(1rho)-weighted MRI pulse sequence. Imaging experiments were performed on a GE clinical scanner with a custom-built knee-coil. We validated the performance of this sequence by imaging articular cartilage of a bovine patella and comparing T(1rho) values measured by this sequence to those obtained with a previously tested two-dimensional imaging sequence. Using a previously developed model for SAR calculation, the imaging parameters were adjusted such that the energy deposition by the radiofrequency pulses in the sequence did not exceed safety guidelines for imaging human subjects. The actual temperature increase due to the sequence was measured in a phantom by a MRI-based temperature mapping technique. Following these experiments, the performance of this sequence was demonstrated in vivo by obtaining T(1rho)-weighted images of the knee joint of a healthy individual. RESULTS: Calculated T(1rho) of articular cartilage in the specimen was similar for both and three-dimensional and two-dimensional methods (84 +/- 2 msec and 80 +/- 3 msec, respectively). The temperature increase in the phantom resulting from the sequence was 0.015 degrees C, which is well below the established safety guidelines. Images of the human knee joint in vivo demonstrate a clear delineation of cartilage from surrounding tissues. CONCLUSION: We developed and implemented a three-dimensional T(1rho)-weighted pulse sequence on a 1.5-T clinical scanner.

Adult↗

PubMed2003

Detection of the anoxic depolarization of focal ischemia using manganese-enhanced MRI.

Mismatch between diffusion- and perfusion-weighted MRI was used to indicate a treatable area following focal ischemia, called the penumbra. Activity-induced manganese contrast MRI has been reported as a new visualization method for neural activation using manganese ions as a depolarization-dependent contrast agent. It is well known that energy failure induced by cerebral ischemia produces anoxic depolarization. The purpose of this study was to detect manganese accumulation caused by permanent middle cerebral artery occlusion (MCAO) of rat brain and to compare regional differences between manganese accumulation and decreased apparent diffusion coefficient (ADC). The ratios of signal intensity of manganese-enhanced MRI in the ipsilateral cortex to that in the contralateral cortex were 171.0 +/- 17.5% in MCAO group and 108.4 +/- 13.2% in the sham group. In addition, the enhanced region was much smaller than the area which was detected as having a reduced ADC.

Animals↗

PubMed2002

Effect of IL-1beta-induced macromolecular depletion on residual quadrupolar interaction in articular cartilage.

PURPOSE: Sodium multiple-quantum filtered (MQF) NMR spectroscopy may potentially be used to measure proteoglycan (PG) depletion in cartilage caused by osteoarthritis (OA). The purpose of this work was to quantify the effect of interleukin-1 (IL-1beta)-induced macromolecule depletion on the residual quadrupolar interaction (RQI) of sodium in bovine cartilage plugs. MATERIALS AND METHODS: Fifteen 8-mm-diameter cartilage plug specimens were cored from the articular surface of fresh bovine patellae. All plugs were kept in culture media and nine of the plugs were subjected to interleukin-1 (IL-1beta)-induced degeneration of cartilage for 4, 6, and 7 days. Sodium NMR spectra were obtained from each sample with a 1-cm-diameter solenoid coil in a 2T whole-body magnet interfaced to a custom-built spectrometer. We employed a previously described theoretical model to analyze triple-quantum filtered (TQF) and double-quantum filtered magic angle (DQFMA) spectra obtained from normal cartilage and cartilage treated with IL-1beta. The model assumes a static Gaussian distribution of the RQI frequency, omega(Q), in the sample. TQF and DQFMA spectra from each sample were fitted with the appropriate signal expressions to determine sigma (the root mean square (RMS) omegaQ), T2f, and T2s. An inversion-recovery sequence was used to determine T1 of each plug. A spectrophotometric assay was used to determine the amount of PG depleted from each plug. Histology was performed to visualize the PG loss in cartilage plugs. We defined sigma as the measure of changes in macroscopic order in the tissue. RESULTS: Simulated spectra from the theoretical model were in excellent agreement with the experimental data. We were able to determine the relaxation times as well as sigma of each specimen from their corresponding fits. T2f ranged between 2.26-3.50 msec, decreasing with increased PG loss. Over the range of PG depletion investigated, T2s increased from 12.3 msec to 14.9 msec, and T1 increased from 16 msec to 21 msec, while sigma decreased from 180 Hz to 120 Hz. The order of macromolecules in the cartilage tissue decreased substantially with PG loss. Histology sections clearly showed qualitative visualization of the PG loss in cartilage following treatment with IL-1beta. CONCLUSION: We demonstrated that IL-beta-induced macromolecule depletion in cartilage not only changes the relaxation characteristics of sodium but also changes RQI of the tissue. Using MQF sodium spectroscopy we quantified the changes in sigma and showed that loss of macromolecules reduces the degree of order in the tissue.

Animals↗

PubMed2002

23Na MRI accurately measures fixed charge density in articular cartilage.

One of the initiating steps of osteoarthritis is the loss of proteoglycan (PG) molecules from the cartilage matrix. One method for assessing cartilage integrity, therefore, is to measure the PG content or fixed charge density (FCD) of cartilage. This report shows the feasibility of calculating FCD by (23)Na MRI and introduces MRI protocols for human studies, in vivo. (23)Na MRI was used to measure the sodium concentration inside bovine patellar cartilage. The sodium concentration was then converted to FCD (mM) by considering ideal Donnan equilibrium. These FCD measurements were compared to FCD measurements obtained through standard dimethylmethylene blue PG assays. There was a high correlation (slope = 0.89, r(2) = 0.81) between the FCD measurements obtained by (23)Na MRI and those obtained by the PG assays. These methods were then employed in quantifying the FCD of articular cartilage of human volunteers in vivo. Two imaging protocols were compared: one using a birdcage coil, the other using a transmit/receive surface coil. Both methodologies gave similar results, with the average sodium concentration of normal human patellar cartilage ranging from approximately 240 to 260 mM. This corresponds to FCDs of -158 mM to -182 mM.

Animals↗

PubMed2002

Fast MRI of RF heating via phase difference mapping.

A method is presented for the rapid acquisition of temperature maps derived from phase difference maps. The temperature-dependent chemical shift coefficients (TDCSCs) of various concentrations of aqueous cobalt and dysprosium-based compounds were measured. The largest TDCSC calculated was for 100 mM DyEDTA, which had a TDCSC of -0.09 PPM/K; 160 mM CoCl2 had a TDCSC of -0.04 PPM/K. These temperature-dependent chemical shifts (TDCSs) result in phase changes in the MR signal with changing temperature. Agarose phantoms were constructed with each paramagnetic metal. A fast gradient-echo (FGRE) MR image was acquired to serve as the baseline image. A "test" MRI procedure was then performed on the phantom. Immediately afterwards, a second FGRE MR image was acquired, serving as the probing image. Proper image processing as a phase difference map between the probing image and the baseline image resulted in an image which quantitatively described the temperature increase of the phantom in response to a particular "test" imaging experiment. Applications of this technique in assessing the safety of pulse sequences and MR coils are discussed.

Biophysical Phenomena↗

PubMed2002

Quantifying sodium in the human wrist in vivo by using MR imaging.

The authors quantified sodium content in the wrist joints of six healthy volunteers with no known history of arthritis or pain. Average sodium concentrations ranged from 115 to 150 mmol/L in noncartilaginous regions and from 200 to 210 mmol/L in cartilaginous regions. The feasibility of quantifying sodium in vivo was demonstrated. This method has potential applications in monitoring the integrity of cartilaginous tissue in vivo.

Adult↗