Tomography, Volume 1, Issue 2 (December 2015) – 10 articles

Spatially nonuniform diffusion weighting bias as a result of gradient nonlinearity (GNL) causes substantial errors in apparent diffusion coefficient (ADC) maps for anatomical regions imaged distant from the magnet isocenter. Our previously described approach effectively removed spatial ADC bias from 3 orthogonal diffusion-weighted imaging (DWI) measurements for monoexponential media of arbitrary anisotropy. This work evaluates correction feasibility and performance for quantitative diffusion parameters of the 2-component intravoxel incoherent motion (IVIM) model for well-perfused and nearly isotropic renal tissue. Sagittal kidney DWI scans of a volunteer were performed on a clinical 3T magnetic resonance imaging scanner near isocenter and offset superiorly. Spatially nonuniform diffusion weighting caused by GNL resulted both in shifting and broadening of perfusion-suppressed ADC histograms for off-center DWI relative to unbiased measurements close to the isocenter. Direction-average diffusion weighting bias correctors were computed based on the known gradient design provided by the vendor. The computed bias maps were empirically confirmed by coronal DWI measurements for an isotropic gel-flood phantom. Both phantom and renal tissue ADC bias for off-center measurements was effectively removed by applying precomputed 3D correction maps. Comparable ADC accuracy was achieved for corrections of both b maps and DWI intensities in the presence of IVIM perfusion. No significant bias impact was observed for the IVIM perfusion fraction. Full article

Magnetic resonance fingerprinting (MRF) is an imaging tool that produces multiple magnetic resonance imaging parametric maps from a single scan. Herein we describe the normal range and progression of MRF-derived relaxometry values with age in healthy individuals. In total, 56 normal volunteers (24 men and 32 women) aged 11–71 years were scanned. Regions of interest were drawn on T₁ and T₂ maps in 38 areas, including lobar and deep white matter (WM), deep gray nuclei, thalami, and posterior fossa structures. Relaxometry differences were assessed using a forward stepwise selection of a baseline model that included either sex, age, or both, where variables were included if they contributed significantly (p < 0.05). In addition, differences in regional anatomy, including comparisons between hemispheres and between anatomical subcomponents, were assessed by paired t tests. MRF-derived T₁ and T₂ in frontal WM regions increased with age, whereas occipital and temporal regions remained relatively stable. Deep gray nuclei such as substantia nigra, were found to have agerelated decreases in relaxometry. Differences in sex were observed in T₁ and T₂ of temporal regions, the cerebellum, and pons. Men were found to have more rapid age-related changes in frontal and parietal WM. Regional differences were identified between hemispheres, between the genu and splenium of the corpus callosum, and between posteromedial and anterolateral thalami. In conclusion, MRF quantification measures relaxometry trends in healthy individuals that are in agreement with the current understanding of neurobiology and has the ability to uncover additional patterns that have not yet been explored. Full article

Tissue conductivity is a biophysical marker of tissue structure and physiology. Present methods of measuring tissue conductivity are limited. Electrical impedance tomography and magnetic resonance electrical impedance tomography rely on passing an external current through the object being imaged, which prevents its use in most human imaging. More recently, tissue conductivity has been determined noninvasively from measurements of the radiofrequency (RF) field used in magnetic resonance imaging (MRI). This technique is promising, but conductivity at higher frequencies is less sensitive to tissue structure. Measuring tissue conductivity noninvasively at low frequencies remains elusive. It has been proposed that eddy currents generated during the rise and decay of gradient pulses could act as a current source to map low-frequency conductivity. This work centers on a gradient echo pulse sequence that uses large gradients before excitation to create eddy currents. The electric and magnetic fields during a gradient pulse are simulated by a finite-difference timedomain simulation. The sequence is also tested with a phantom and animal MRI scanner equipped with gradients of high gradient strengths and slew rates. The simulation demonstrates that eddy currents in materials with a conductivity similar to biological tissue decay with a half-life on the order of nanoseconds, and any eddy currents generated before excitation decay completely before influencing the RF signal. Gradient-induced eddy currents can influence phase accumulation after excitation, but the effect is too small to image. The animal scanner images show no measurable phase accumulation. Measuring low-frequency conductivity by gradient-induced eddy currents is presently unfeasible. Full article

Genetically encoded fluorescence resonance energy transfer (FRET) reporters are powerful tools for analyzing cell signaling and function at single-cell resolution in standard 2D cell cultures, but these reporters rarely have been applied to 3D environments. FRET interactions between donor and acceptor molecules typically are determined by changes in relative fluorescence intensities, but wavelength-dependent differences in light absorption complicate this analysis method in 3D settings. Herein we report fluorescence lifetime imaging microscopy (FLIM) with phasor analysis, a method that displays fluorescence lifetimes on a pixel-wise basis in real time to quantify apoptosis in breast cancer cells stably expressing a genetically encoded FRET reporter. This microscopic imaging technology allowed us to identify treatment-induced apoptosis in single breast cancer cells in environments ranging from 2D cell culture, spheroids with cancer and bone marrow stromal cells, and living mice with orthotopic human breast cancer xenografts. Using this imaging strategy, we showed that combined metabolic therapy targeting glycolysis and glutamine pathways significantly reduced overall breast cancer metabolism and induced apoptosis. We also determined that distinct subpopulations of bone marrow stromal cells control the resistance of breast cancer cells to chemotherapy, suggesting heterogeneity of treatment responses of malignant cells in different bone marrow niches. Overall, this study establishes FLIM with phasor analysis as an imaging tool for apoptosis in cell-based assays and living mice, enabling real-time, cellular-level assessment of treatment efficacy and heterogeneity. Full article

Recent animal studies have shown that D-glucose is a potential biodegradable magnetic resonance imaging (MRI) contrast agent for imaging glucose uptake in tumors. We show herein the first translation of that use of D-glucose to human studies. Chemical exchange saturation transfer (CEST) MRI at a single frequency offset optimized for detecting hydroxyl protons in D-glucose was used to image dynamic signal changes in the human brain at 7 T during and after D-glucose infusion. Dynamic glucose enhanced (DGE) image data from 4 normal volunteers and 3 glioma patients showed a strong signal enhancement in blood vessels, while a spatially varying enhancement was found in tumors. Areas of enhancement differed spatially between DGE and conventional gadolinium-enhanced imaging, suggesting complementary image information content for these 2 types of agents. In addition, different tumor areas enhanced with D-glucose at different times after infusion, suggesting a sensitivity to perfusion-related properties such as substrate delivery and blood-brain barrier (BBB) permeability. These preliminary results suggest that DGE MRI is feasible for studying glucose uptake in humans, providing a time-dependent set of data that contains information regarding arterial input function, tissue perfusion, glucose transport across the BBB and cell membrane, and glucose metabolism. Full article

Pathologic vertebral compression fractures (PVCFs) cause significant morbidity in patients with metastatic bone disease. Limitations in existing clinical biomarkers leave clinicians without reliable metrics for predicting PVCF, thus impeding efforts to prevent this severe complication. To establish the feasibility of a new method for defining the risk of a PVCF, we retrospectively analyzed serial computed tomography (CT) scans from 5 breast cancer patients using parametric response mapping (PRM) to quantify dynamic bone miniral density (BMD) changes that preceded an event. Vertebrae segmented from each scan were registered to the same spatial frame and voxel classification was accomplished using a predetermined threshold of change in Hounsfield units (HU), resulting in relative volumes of increased (PRM_HU+), decreased (PRM_HU−), or unchanged (PRM_HU0) attenuation. A total of 7 PVCFs were compared to undiseased vertebrae in each patient serving as controls. A receiver operator curve (ROC) analysis identified optimal imaging times for group stratification. BMD changes were apparent by an elevated PRM_HU+ as early as 1 year before fracture. ROC analysis showed poor performance of PRM_HU− in stratifying PVCFs versus controls. As early as 6 months before PVCF, PRM_HU+ was significantly larger (12.9 ± 11.6%) than control vertebrae (2.3 ± 2.5%), with an area under the curve of 0.918 from an ROC analysis. Mean HU changes were also significant between PVCF (26.8 ± 26.9%) and control (−2.2 ± 22.0%) over the same period. A PRM analysis of BMD changes using standard CT imaging was sensitive for spatially resolving changes that preceded structural failure in these patients. Full article

Magnetic labeling of stem cells enables their noninvasive detection by magnetic resonance imaging (MRI). In practical terms, most MRI studies have been limited to the visualization of local engraftment because other sources of endogenous hypointense contrast complicate the interpretation of systemic (whole-body) cell distribution. In addition, MRI cell tracking is inherently nonquantitative in nature. We report herein on the potential of magnetic particle imaging (MPI) as a novel tomographic technique for noninvasive “hot-spot” imaging and quantification of stem cells using superparamagnetic iron oxide (SPIO) tracers. Neural and mesenchymal stem cells, representing small and larger cell bodies, were labeled with 3 different SPIO tracer formulations, including 2 preparations (Feridex and Resovist) that have previously been used in clinical MRI celltracking studies. Magnetic particle spectroscopy measurements demonstrated a linear correlation between MPI signal and iron content for both free particles in homogeneous solution and for internalized and aggregated particles in labeled cells over a wide range of concentrations. The overall MPI signal ranged from 1 × 10⁻³ to 3 × 10⁻⁴ Am²/g Fe, which was equivalent to 2 × 10⁻¹⁴ to 1 × 10⁻¹⁵ Am² per cell, indicating that cell numbers can be quantified with MPI analogous to the use of radiotracers in nuclear medicine or fluorine tracers in 19F MRI. When SPIO-labeled cells were transplanted in the mouse brain, they could be readily detected by MPI at a detection threshold of about 5 × 104 cells, with MPI/MRI overlays showing an excellent agreement between the hypointense MRI areas and MPI hot spots. The calculated tissue MPI signal ratio for 100,000 vs 50,000 implanted cells was 2.08. Hence, MPI can potentially be further developed for quantitative and easy-to-interpret, tracer-based noninvasive cell imaging, preferably with MRI as an adjunct anatomical imaging modality. Full article

Image blurring that results from off-resonance and fast T₂* signal decay is a common issue in radial ultrashort echo time magnetic resonance imaging (MRI) sequences. One solution is to use a higher readout bandwidth, but this may be impractical for some techniques such as pointwise-encoding time reduction with radial acquisition (PETRA), which is a hybrid method of zero echo time and single-point imaging techniques. Specifically, PETRA has severe specific absorption rate (SAR) and radiofrequency (RF) pulse peak power limitations when using higher bandwidths in human measurements. In this study, we introduce gradient modulation (GM) to PETRA to reduce image-blurring artifacts while keeping SAR and RF peak power low. GM-PETRA tolerance to image blurring was evaluated in simulations and experiments by comparison with the conventional PETRA technique. We performed inner ear imaging of a healthy subject at 7 T. GM-PETRA showed significantly less image blurring as a result of off-resonance and fast T₂* signal decay compared to PETRA. In in vivo imaging, GM-PETRA nicely captured complex structures of the inner ear such as the cochlea and semicircular canals. GM can improve PETRA image quality and mitigate SAR and RF peak power limitations without special hardware modification in clinical scanners. Full article

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging is an emerging technique for evaluating patients with prostate cancer (PCa) in a variety of clinical contexts. As with any new imaging modality, there are interpretive pitfalls that are beginning to be recognized. In this report, we describe the findings in a 63-year-old male with biochemically recurrent PCa after radical prostatectomy who was imaged with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid ([¹⁸F]DCFPyL), a small-molecule inhibitor of PSMA. Diffuse radiotracer uptake was noted throughout the sacrum, corresponding to imaging findings on contrast-enhanced computed tomography (CT), bone scan, and pelvic magnetic resonance imaging consistent with Paget's disease of bone. The uptake of [¹⁸F]DCFPyL in Paget's disease most likely results from hyperemia and increased radiotracer delivery. In light of the overlap in patients affected by PCa and Paget's disease, it is important for nuclear medicine physicians and radiologists to be aware of the potential for this diagnostic pitfall when interpreting PSMA PET/CT scans. Correlating findings on conventional imaging such as diagnostic CT and bone scan can help confirm the diagnosis. Full article