Tomography, Volume 2, Issue 3 (September 2016) – 10 articles

Prior reports have suggested that delayed ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) oncology imaging can improve the contrast-to-noise ratio (CNR) for known lesions. Our goal was to estimaterealistic bounds for lesion detectability for static measurements within 1 to 4 hours between FDG injectionand image acquisition. Tumor and normal tissue kinetic model parameters were estimated from dynamic PETstudies of patients with early-stage breast cancer. These parameters were used to generate time-activitycurves (TACs) for up to 4 hours, for which we assumed both nonreversible and reversible models with differ-ent rates of FDG dephosphorylation (k₄). For each pair of tumor and normal tissue TACs, 600 PET sinogramrealizations were generated, and images were reconstructed using the ordered subsets expectation maximi-zation reconstruction algorithm. Test statistics for each tumor and normal tissue region of interest were outputfrom the computer model observers and evaluated using a receiver operating characteristic analysis, with thecalculated area under the curve (AUC) providing a measure of lesion detectability. For the nonreversiblemodel (k₄ = 0), the AUC increased in 11 of 23 (48%) patients for 1 to 2 hours after the current standardpostradiotracer injection imaging window of 1 hour. This improvement was driven by increased tumor/nor-mal tissue contrast before the impact of increased noise that resulted from radiotracer decay began to domi-nate the imaging signal. Ask4was increased from 0 to 0.01 min⁻¹, the time of maximum detectabilityshifted earlier, due to decreasing FDG concentration in the tumor lowering the CNR. These results imply thatdelayed PET imaging may reveal inconspicuous lesions that otherwise would have gone undetected. Full article

High-grade gliomas are often characterized by hypoxia, which is associated with both poor long-term prognosis and therapy resistance. The adverse role hypoxia plays in treatment resistance and disease progression has led to the development of hypoxia imaging methods and hypoxia-targeted treatments. Here, we determined the tumor hypoxia and vascular perfusion characteristics of 2 rat orthotopic glioma models using 18-fluoromisonidozole positron emission tomography. In addition, we determined tumor response to the hypoxia-activated prodrug evofosfamide (TH-302) in these rat glioma models. C6 tumors exhibited more hypoxia and were less perfused than 9L tumors. On the basis of these differences in their tumor hypoxic burden, treatment with evofosfamide resulted in 4- and 2-fold decreases in tumor growth rates of C6 and 9L tumors, respectively. This work shows that imaging methods sensitive to tumor hypoxia and perfusion are able to predict response to hypoxia-targeted agents. This has implications for improved patient selection, particularly in clinical trials, for treatment with hypoxia-activated cytotoxic prodrugs, such as evofosfamide. Full article

Magnetic resonance imaging (MRI) is used to diagnose and monitor brain tumors. Extracting additional information from medical imaging and relating it to a clinical variable of interest is broadly defined as radiomics. Here, multiparametric MRI radiomic profiles (RPs) of de novo glioblastoma (GBM) brain tumors is related with patient prognosis. Clinical imaging from 81 patients with GBM before surgery was analyzed. Four MRI contrasts were aligned, masked by margins defined by gadolinium contrast enhancement and T2/fluid attenuated inversion recovery hyperintensity, and contoured based on image intensity. These segmentations were combined for visualization and quantification by assigning a 4-digit numerical code to each voxel to indicate the segmented RP. Each RP volume was then compared with overall survival. A combined classifier was then generated on the basis of significant RPs and optimized volume thresholds. Five RPs were predictive of overall survival before therapy. Combining the RP classifiers into a single prognostic score predicted patient survival better than each alone (P < .005). Voxels coded with 1 RP associated with poor prognosis were pathologically confirmed to contain hypercellular tumor. This study applies radiomic profiling to de novo patients with GBM to determine imaging signatures associated with poor prognosis at tumor diagnosis. This tool may be useful for planning surgical resection or radiation treatment margins. Full article

Despite major advances in targeted drug therapy and radiation therapy, surgery remains the most effective treatment for most solid tumors. The single most important predictor of patient survival is a complete surgical resection of the primary tumor, draining lymph nodes, and metastatic lesions. Presently, however, 20%–30% of patients with head and neck cancer who undergo surgery still leave the operating room without complete resection because of missed lesions. Thus, major opportunities exist to develop advanced imaging tracers and intraoperative instrumentation that would allow surgeons to visualize microscopic tumors during surgery. The cell adhesion molecule integrin αvβ3 is specifically expressed by tumor neovasculature and invading tumor cells, but not by quiescent vessels or normal cells. Here we report the combined use of an integrin-targeting near-infrared tracer (RGD-IRDye800CW) and a handheld spectroscopic device, an integrated point spectroscopy with wide-field imaging system, for highly sensitive detection of integrin overexpression on infiltrating cancer cells. By using an orthotopic head and neck cancer animal model, we show that this tracer–device combination allows intraoperative detection of not only invasive tumor margins but also metastatic lymph nodes. Correlated histological analysis further reveals that microscopic clusters of 50–100 tumor cells can be detected intraoperatively with high sensitivity and specificity, raising new possibilities in guiding surgical resection of microscopic tumors and metastatic lymph nodes. Full article

Noninvasive quantification of subject-specific low-frequency brain tissue conductivity (σ_LF) will be valuable in different fields, for example, neuroscience. Magnetic resonance (MR)-electrical impedance tomography allows measurements of σ_LF. However, the required high level of direct current injection leads to an undesirable pain sensation. Following the same principles, but avoiding pain sensation, we evaluate the feasibility of inductively inducing currents using a transcranial magnetic stimulation (TMS) device and recording the magnetic field variations arising from the induced tissue eddy currents using a standard 3 T MR scanner. Using simulations, we characterize the strength of the incident TMS magnetic field arising from the current running in the TMS coil, the strength of the induced magnetic field arising from the induced currents in tissues by TMS pulses, and the MR phase accuracy required to measure this latter magnetic field containing information about σ_LF. Then, using TMS-MRI measurements, we evaluate the achievable phase accuracy for a typical TMS-MRI setup. From measurements and simulations, it is crucial to discriminate the incident from the induced magnetic field. The incident TMS magnetic field range is ±10⁻⁴ T, measurable with standard MR scanners. In contrast, the induced TMS magnetic field is much weaker (±10⁻⁸ T), leading to an MR phase contribution of ∼10⁻⁴ rad. This phase range is too small to be measured, as the phase accuracy for TMS-MRI experiments is ∼10⁻² rads. Thus, although highly attractive, noninvasive measurements of the induced TMS magnetic field, and therefore estimations of σLF, are experimentally not feasible. Full article

In this study, we develop a classification system for describing polymethyl methacrylate (PMMA) spread in vertebral bodies after kyphoplasty or vertebroplasty for vertebral compression fractures (VCFs) and for assessing whether PMMA spread varies between operators, VCF etiology, or vertebral level. Intraoperative fluoroscopic images of 198 vertebral levels were reviewed in 137 patients (women, 84; men, 53; mean age, 75.8 ± 12.5; and those with a diagnosis of osteoporosis, 63%) treated with kyphoplasty between January 01, 2015 and May 31, 2015 at a single center to create a 5-class descriptive system. PMMA spread patterns in the same images were then classified by 2 board-certified radiologists, and a third board-certified radiologist resolved conflicts. A total of 2 primary PMMA spread patterns were identified, namely, acinar and globular, with subtypes of localized acinar, diffuse globular, and mixed, to describe an equal combination of patterns. Interrater reliability using the system was moderate (κ = 0.47). After resolving conflicts, the most common spread class was globular (n = 63), followed by mixed (n = 58), diffuse globular (n = 30), acinar (n = 27), and localized acinar (n = 20). The spread class after treatment by the 2 most frequent operators differed significantly (n₁ = 63, n₂ = 70; P < .0001). There was no difference in the spread class between VCF etiologies or vertebral levels. PMMA spread may, therefore, be a modifiable parameter that affects kyphoplasty and vertebroplasty efficacy and adverse events. Full article

Quantitative hepatic perfusion parameters derived by fitting dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of liver to a pharmacokinetic model are prone to errors if the dynamic images are not corrected for respiratory motion by image registration. The contrast-induced intensity variations in pre- and postcontrast phases pose challenges for the accuracy of image registration. We propose an overdetermined system of transformation equations between the image volumes in the DCE-MRI series to achieve robust alignment. In this method, we register each volume to every other volume. From the transforms produced by all pairwise registrations, we constructed an overdetermined system of transform equations that was solved robustly by minimizing the L_1/2-norm of the residuals. This method was evaluated on a set of 100 liver DCE-MRI examinations from 35 patients by examining the area under spikes appearing in the voxel time–intensity curves. The robust alignment procedure significantly reduced the area under intensity spikes compared with unregistered volumes (P < .001) and volumes registered to a single reference phase (P < .001). Our registration procedure provides a larger number of reliable time–intensity curve samples. The additional reliable samples in the precontrast baseline are important for calculating the postcontrast signal enhancement and thereby for converting intensity to contrast concentration. On the intensity ramp, retained samples help to better describe the uptake dynamics, providing a better foundation for parameter estimation. The presented method also simplifies the analysis of data sets with many patients by eliminating the need for manual intervention during registration. Full article

Recently, a growing interest has been seen in the development of T₁–T₂ dual-mode probes that can simultaneously enhance contrast on T₁- and T₂-weighted images. A common strategy is to integrate T₁ and T₂ components in a decoupled manner into a nanoscale particle. This approach, however, often requires a multi-step synthesis and delicate nanoengineering, which may potentially affect the production and wide application of the probes. We herein report the facile synthesis of a 50-nm nanoscale metal–organic framework (NMOF) comprising gadolinium (Gd³⁺) and europium (Eu³⁺) as metallic nodes. These nanoparticles can be prepared in large quantities and can be easily coated with a layer of silica. The yielded Eu,Gd-NMOF@SiO₂ nanoparticles are less toxic, highly fluorescent, and afford high longitudinal (38 mM⁻¹s⁻¹) and transversal (222 mM⁻¹s⁻¹) relaxivities on a 7 T magnet. The nanoparticles were conjugated with c(RGDyK), a tumor-targeting peptide sequence, which has a high binding affinity toward integrin α_vβ₃. Eu,Gd-NMOF@SiO₂ nanoparticles, when intratumorally or intravenously injected, induce simultaneous signal enhancement and signal attenuation on T₁-and T₂-weighted images, respectively. These results suggest great potential of the NMOFs as a novel T₁–T₂ dual-mode contrast agent. Full article

Oxidized regenerated cellulose (ORC) is a commonly used surgical hemostatic agent. When retained at the surgical site, it is frequently misdiagnosed on postoperative computed tomography (CT) images as an abscess or a recurrent tumor. Oxidized nonregenerated cellulose (ONC) is a new, more effective version of ORC. It is more effective because of its unorganized fiber structure and greater material density, which may also alter its appearance on CT images relative to ORC. This image report compares the CT characteristics of ONC and ORC. A rabbit's bilateral femoral arteries were punctured to model peripheral vascular surgery. ORC was used to treat 1 of the femoral artery punctures and ONC to treat the contralateral puncture. Noncontrast CT imaging was performed immediately following surgery (day 0) and on postoperative day 14. On day 0, both ORC and ONC were isoattenuating relative to muscle and hyperattenuating to fat, although ONC appears more homogenous. On day 14, neither ORC nor ONC was clearly identifiable. Thus, postoperative retention of ONC can obscure immediate postoperative CT interpretation and, similar to ORC, lead to an erroneous diagnosis of an abscess. By day 14, ONC retention may not obscure CT interpretation. In noncontrast CT imaging, ONC appears more homogeneous than ORC, but is otherwise indistinguishable. The greater homogeneity of ONC may be caused by the unorganized fiber structure or greater material density. Intraoperative use of ONC should be clinically investigated before radiographically diagnosing a postoperative abscess or recurrent tumor. Full article

Cardiac magnetic resonance imaging at ultra-high field (B₀ ≥ 7 T) potentially provides improved resolution and new opportunities for tissue characterization. Although an accurate synchronization of the acquisition to the cardiac cycle is essential, electrocardiogram (ECG) triggering at ultra-high field can be significantly impacted by the magnetohydrodynamic (MHD) effect. Blood flow within a static magnetic field induces a voltage, which superimposes the ECG and often affects the recognition of the R-wave. The MHD effect scales with B₀ and is particularly pronounced at ultra-high field creating triggering-related image artifacts. Here, we investigated the performance of a conventional 3-lead ECG trigger device and a state-of-the-art trigger algorithm for cardiac ECG synchronization at 7 T. We show that by appropriate subject preparation and by including a learning phase for the R-wave detection outside of the magnetic field, reliable ECG triggering is feasible in healthy subjects at 7 T without additional equipment. Ultra-high field cardiac imaging was performed with the ECG signal and the trigger events recorded in 8 healthy subjects. Despite severe ECG signal distortions, synchronized imaging was successfully performed. Recorded ECG signals, vectorcardiograms, and large consistency in trigger event spacing indicate high accuracy for R-wave detection. Full article