Tomography, Volume 2, Issue 1 (March 2016) – 9 articles

Myelofibrosis (MF) is a hematologic neoplasm arising as a primary disease or secondary to other blood malignancies. Both primary and secondary MF develop progressive fibrosis of bone marrow, displacing normal hematopoietic cells to other organs and disrupting normal production of mature blood cells. Activation of JAK2 signaling in hematopoietic stem cells commonly causes MF, and ruxolitinib, a drug targeting this pathway, is the preferred treatment for many patients. However, current measures of disease status in MF do not necessarily predict response to treatment with ruxolitinib or other drugs. Bone marrow biopsies are invasive and prone to sampling error, while measurements of spleen volume only indirectly reflect status of bone marrow. Toward the goal of developing an imaging biomarker for treatment response in MF, we present preliminary results from a prospective clinical study evaluating parametric response mapping (PRM) of quantitative Dixon MRI bone marrow fat fraction maps in four MF patients treated with ruxolitinib. PRM allows voxel-wise identification of temporal changes in quantitative imaging readouts, in this case bone marrow fat. We identified heterogeneous responses of bone marrow fat among patients and within different bone marrow sites in the same patient. Changes in bone marrow fat fraction also were discordant with reductions in spleen volume, the standard imaging metric for treatment response. This study provides initial support for PRM analysis of quantitative MRI of bone marrow fat to monitor therapy in MF, setting the stage for larger studies to further develop and validate this method as a complementary imaging biomarker. Full article

Pharmacokinetic analysis of dynamic contrast-enhanced (DCE) MRI data allows estimation of quantitative imaging biomarkers such as K^trans (rate constant for plasma/interstitium contrast reagent (CR) transfer) and v_e (extravascular and extracellular volume fraction). However, the use of quantitative DCE-MRI in clinical practice is limited with uncertainty in arterial input function (AIF) determination being one of the primary reasons. In this multicenter study to assess the effects of AIF variations on pharmacokinetic parameter estimation, DCE-MRI data acquired at one center from 11 prostate cancer patients were shared among nine centers. Individual AIF from each data set was determined by each center and submitted to the managing center. These AIFs, along with a literature population averaged AIF, and their reference-tissue-adjusted variants were used by the managing center to perform pharmacokinetic data analysis using the Tofts model (TM). All other variables, including tumor region of interest (ROI) definition and pre-contrast T1, were kept constant to evaluate parameter variations caused solely by AIF discrepancies. Considerable parameter variations were observed with the within-subject coefficient of variation (wCV) of K^trans obtained with unadjusted AIFs being as high as 0.74. AIF-caused variations were larger in K^trans than v_e and both were reduced when reference-tissue-adjusted AIFs were used. These variations were largely systematic, resulting in nearly unchanged parametric map patterns. The intravasation rate constant, kep (= K^trans/v_e), was less sensitive to AIF variation than Ktrans (wCV for unadjusted AIFs: 0.45 vs. 0.74), suggesting that it might be a more robust imaging biomarker of prostate microvasculature than Ktrans. Full article

Proton magnetic resonance imaging (¹H MRI) of gases can potentially enable functional lung imaging to probe gas ventilation and other functions. Here, ¹H MR images of hyperpolarized (HP) and thermally polarized propane gas were obtained using ultrashort echo time (UTE) pulse sequence. A 2-dimensional (2D) image of thermally polarized propane gas with ∼0.9 × 0.9 mm² spatial resolution was obtained in <2 seconds, showing that even non-HP hydrocarbon gases can be successfully used for conventional proton magnetic resonance imaging. The experiments were also performed with HP propane gas, and high-resolution multislice FLASH 2D images in ∼510 seconds and non-slice-selective 2D UTE MRI images were acquired in ∼2 seconds. The UTE approach adopted in this study can be potentially used for medical lung imaging. Furthermore, the possibility of combining UTE with selective suppression of 1H signals from 1 of the 2 gases in a mixture is shown in this MRI study. The latter can be useful for visualizing industrially important processes where several gases may be present, eg, gas–solid catalytic reactions. Full article

We aim to focus on improving the performance of slice parallel imaging while simultaneously correcting for spatial shift artifacts related to off-resonance. In multislice controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA), simultaneously excited slices are shifted along the phase-encoding direction by varying the radiofrequency phase for each slice, thereby obtaining virtually shifted coil sensitivity information. Meanwhile, the view angle tilting (VAT) technique provides additional shifts in the readout direction to further spread an image overlap while correcting for field inhomogeneity-induced spatial misregistration using a compensation gradient. By combining these features of CAIPIRINHA and VAT, named CAIPIVAT, the excited individual slices are shifted along both phase-encoding and readout directions. Consequently, the number of aliased voxels is reduced, and the virtual coil sensitivity information is more effectively used. Blurring due to the compensation gradient in VAT was alleviated by using a constrained least square filter. The advantages of CAIPIVAT are shown by signal-to-noise ratio simulation, phantom experiments, and in vivo experiments. Thus, CAIPIVAT can be useful for multislice parallel imaging while providing the correction of off-resonance-related spatial shift artifact. Full article

Incidental detection of localized renal tumors at imaging is increasing. Conventional imaging cannot reliably differentiate the 20% of these tumors that are benign from malignant renal cell carcinomas (RCCs), leading to unnecessary surgical resection and resulting morbidity. Here, we investigated hyperpolarized ¹³C pyruvate metabolism in live patient-derived renal tumor tissue slices using a novel magnetic resonance-compatible bioreactor platform. We show, for the first time, that clear cell RCCs (ccRCCs), which constitute 70%–80% of all RCCs, exhibit increased lactate production and rapid lactate efflux when compared with benign renal tumors. This difference is because of increased lactate dehydrogenase A and monocarboxylate transporter 4 expression in ccRCCs. Thus, RCCs can be differentiated from benign renal tumors by assessing this distinctive metabolic phenotype using clinically translatable hyperpolarized ¹³C pyruvate magnetic resonance. Full article

Iron particles are intravenously (IV) administered to label cells in vivo during magnetic resonance imaging. This technique has been extensively used to monitor immune cells in the context of inflammatory diseases. Here, we have investigated whether resting immune cells can be labeled in vivo in healthy mice before disease onset or injury, thus allowing visualization of critical early cellular events. Using 1.5 T magnetic resonance imaging, we were able to detect signal loss in bone marrow, liver, and spleen as early as 1 hour after the IV injection of superparamagnetic iron oxide nanoparticles (Feridex; 80 to 120 nm in diameter) or larger micron-sized iron oxide particles (Bangs; 0.9 μm in diameter). Results were confirmed via histology. Further, flow cytometric analysis confirmed the presence of iron-labeled CD19⁺ B cells, CD3⁺ T cells, and CD11b⁺ myeloid cells within the spleen and the bone marrow. Extending this work to a murine model of multiple sclerosis, we IV administered superparamagnetic iron oxide to healthy mice 1 week before inducing experimental autoimmune encephalomyelitis. Images acquired 1 week after the onset of hindlimb paralysis showed regions of signal hypointensity in the mouse brain that corresponded with iron-labeled macrophages. In summary, we show that resting immune cells in the healthy mouse liver, spleen, and bone marrow can be prelabeled with iron oxide nanoparticles. Furthermore, iron oxide preloading of immune cells in the reticuloendothelial system can be used to detect cellular infiltration in the brains of experimental autoimmune encephalomyelitis mice. Full article

Planar fluorescence imaging is widely used in biological research because of its simplicity, use of nonionizing radiation, and high-throughput data acquisition. In cancer research, where small animal models are used to study the in vivo effects of cancer therapeutics, the output of interest is often the tumor volume. Unfortunately, inaccuracies in determining tumor volume from surface-weighted projection fluorescence images undermine the data, and alternative physical or conventional tomographic approaches are prone to error or are tedious for most laboratories. Here, we report a method that uses a priori knowledge of a tumor xenograft model, a tumor-targeting near infrared probe, and a custom-developed image analysis planar view tumor volume algorithm (PV-TVA) to estimate tumor volume from planar fluorescence images. Our algorithm processes images obtained using near infrared light for improving imaging depth in tissue in comparison with light in the visible spectrum. We benchmarked our results against the actual tumor volume obtained from a standard water volume displacement method. Compared with a caliper-based method that has an average deviation from an actual volume of 18% (204.34 ± 115.35 mm³), our PV-TVA average deviation from the actual volume was 9% (97.24 ± 70.45 mm³; P < .001). Using a normalization-based analysis, we found that bioluminescence imaging and PV-TVA average deviations from actual volume were 36% and 10%, respectively. The improved accuracy of tumor volume assessment from planar fluorescence images, rapid data analysis, and the ease of archiving images for subsequent retrieval and analysis potentially lend our PV-TVA method to diverse cancer imaging applications. Full article

Nuclear imaging techniques, primarily including positron emission tomography and single-photon emission computed tomography, can provide quantitative information for a biological event in vivo with ultrahigh sensitivity; however, the comparatively low spatial resolution is their major limitation in clinical application. With the convergence of nuclear imaging with other imaging modalities like computed tomography, magnetic resonance imaging, and optical imaging, the hybrid imaging platforms can overcome the limitations of each individual imaging technique. Possessing versatile chemical linking ability and good cargo-loading capacity, radioactive nanomaterials can serve as ideal imaging contrast agents. Here, we provide a brief overview about the current state-of-the-art applications of radioactive nanomaterials in multimodality imaging. We present strategies for incorporation of radioisotope(s) into nanomaterials with the applications of radioactive nanomaterials in multimodal imaging. Advantages and limitations of radioactive nanomaterials for multimodal imaging applications are discussed. Finally, a future perspective of possible radioactive nanomaterial utilization is presented for improving diagnosis and patient management in a variety of diseases. Full article

Publications containing multidimensional image content have traditionally been confined to present information in a static 2-dimensional format. Inclusion of videos within a publication provides enhanced opportunities to present multidimensional image views rather than relying on static images to communicate findings. However, a significant advance is presented, in which an image viewer can be integrated into a digital publication format, allowing for user-manipulated and interactive multidimensional viewing of published image data directly inline with the manuscript. This technological advancement allows for user manipulation and interrogation of multidimensional published image data directly within the scientific article. This capability opens up many new and exciting opportunities for publishing in the field of radiological sciences and beyond. Full article