Amir Pourmorteza

Abdominal Imaging with Contrast-enhanced Photon-counting CT: First Human Experience

PURPOSE To evaluate the performance of a prototype photon-counting detector (PCD) computed tomography (CT) system for abdominal CT in humans and to compare the results with a conventional energy-integrating detector (EID). MATERIALS AND METHODS The study was HIPAA-compliant and institutional review board-approved with informed consent. Fifteen asymptomatic volunteers (seven men; mean age, 58.2 years ± 9.8 [standard deviation]) were prospectively enrolled between September 2 and November 13, 2015. Radiation dose-matched delayed contrast agent-enhanced spiral and axial abdominal EID and PCD scans were acquired. Spiral images were scored for image quality (Wilcoxon signed-rank test) in five regions of interest by three radiologists blinded to the detector system, and the axial scans were used to assess Hounsfield unit accuracy in seven regions of interest (paired t test). Intraclass correlation coefficient (ICC) was used to assess reproducibility. PCD images were also used to calculate iodine concentration maps. Spatial resolution, noise-power spectrum, and Hounsfield unit accuracy of the systems were estimated by using a CT phantom. RESULTS In both systems, scores were similar for image quality (median score, 4; P = .19), noise (median score, 3; P = .30), and artifact (median score, 1; P = .17), with good interrater agreement (image quality, noise, and artifact ICC: 0.84, 0.88, and 0.74, respectively). Hounsfield unit values, spatial resolution, and noise-power spectrum were also similar with the exception of mean Hounsfield unit value in the spinal canal, which was lower in the PCD than the EID images because of beam hardening (20 HU vs 36.5 HU; P < .001). Contrast-to-noise ratio of enhanced kidney tissue was improved with PCD iodine mapping compared with EID (5.2 ± 1.3 vs 4.0 ± 1.3; P < .001). CONCLUSION The performance of PCD showed no statistically significant difference compared with EID when the abdomen was evaluated in a conventional scan mode. PCD provides spectral information, which may be used for material decomposition.

Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors Aid in Functional Recovery of Sensory Pathways following Contusive Spinal Cord Injury

Background Transplantations of human stem cell derivatives have been widely investigated in rodent models for the potential restoration of function of neural pathways after spinal cord injury (SCI). Studies have already demonstrated cells survival following transplantation in SCI. We sought to evaluate survival and potential therapeutic effects of transplanted human embryonic stem (hES) cell-derived oligodendrocyte progenitor cells (OPCs) in a contusive injury in rats. Bioluminescence imaging was utilized to verify survivability of cells up to 4 weeks, and somatosensory evoked potential (SSEPs) were recorded at the cortex to monitor function of sensory pathways throughout the 6-week recovery period. Principal Findings hES cells were transduced with the firefly luciferase gene and differentiated into OPCs. OPCs were transplanted into the lesion epicenter of rat spinal cords 2 hours after inducing a moderate contusive SCI. The hES-treatment group showed improved SSEPs, including increased amplitude and decreased latencies, compared to the control group. The bioluminescence of transplanted OPCs decreased by 97% in the injured spinal cord compared to only 80% when injected into an uninjured spinal cord. Bioluminescence increased in both experimental groups such that by week 3, no statistical difference was detected, signifying that the cells survived and proliferated independent of injury. Post-mortem histology of the spinal cords showed integration of human cells expressing mature oligodendrocyte markers and myelin basic protein without the expression of markers for astrocytes (GFAP) or pluripotent cells (OCT4). Conclusions hES-derived OPCs transplanted 2 hours after contusive SCI survive and differentiate into OLs that produce MBP. Treated rats demonstrated functional improvements in SSEP amplitudes and latencies compared to controls as early as 1 week post-injury. Finally, the hostile injury microenvironment at 2 hours post-injury initially caused increased cell death but did not affect the long-term cell proliferation or survival, indicating that cells can be transplanted sooner than conventionally accepted.

A new method for cardiac computed tomography regional function assessment: stretch quantifier for endocardial engraved zones (SQUEEZ).

Background— Quantitative assessment of regional myocardial function has important diagnostic implications in cardiac disease. Recent advances in CT imaging technology have allowed fine anatomic structures, such as endocardial trabeculae, to be resolved and potentially used as fiducial markers for tracking local wall deformations. We developed a method to detect and track such features on the endocardium to extract a metric that reflects local myocardial contraction. Methods and Results— First-pass CT images and contrast-enhanced cardiovascular magnetic resonance images were acquired in 8 infarcted and 3 healthy pigs. We tracked the left ventricle wall motion by segmenting the blood from myocardium and calculating trajectories of the endocardial features seen on the blood cast. The relative motions of these surface features were used to represent the local contraction of the endocardial surface with a metric we call Stretch Quantifier of Endocardial Engraved Zones (SQUEEZ). The average SQUEEZ value and the rate of change in SQUEEZ were calculated for both infarcted and healthy myocardial regions. SQUEEZ showed a significant difference between infarct and remote regions ( P <0.0001). No significant difference was observed between normal myocardium (noninfarcted hearts) and remote regions ( P =0.8). Conclusions— We present a new quantitative method for measuring regional cardiac function from high-resolution volumetric CT images, which can be acquired during angiography and myocardial perfusion scans. Quantified measures of regional cardiac mechanics in normal and abnormally contracting regions in infarcted hearts were shown to correspond well with noninfarcted and infarcted regions as detected by delayed enhancement cardiovascular magnetic resonance images.Background— Quantitative assessment of regional myocardial function has important diagnostic implications in cardiac disease. Recent advances in CT imaging technology have allowed fine anatomic structures, such as endocardial trabeculae, to be resolved and potentially used as fiducial markers for tracking local wall deformations. We developed a method to detect and track such features on the endocardium to extract a metric that reflects local myocardial contraction. Methods and Results— First-pass CT images and contrast-enhanced cardiovascular magnetic resonance images were acquired in 8 infarcted and 3 healthy pigs. We tracked the left ventricle wall motion by segmenting the blood from myocardium and calculating trajectories of the endocardial features seen on the blood cast. The relative motions of these surface features were used to represent the local contraction of the endocardial surface with a metric we call Stretch Quantifier of Endocardial Engraved Zones (SQUEEZ). The average SQUEEZ value and the rate of change in SQUEEZ were calculated for both infarcted and healthy myocardial regions. SQUEEZ showed a significant difference between infarct and remote regions (P<0.0001). No significant difference was observed between normal myocardium (noninfarcted hearts) and remote regions (P=0.8). Conclusions— We present a new quantitative method for measuring regional cardiac function from high-resolution volumetric CT images, which can be acquired during angiography and myocardial perfusion scans. Quantified measures of regional cardiac mechanics in normal and abnormally contracting regions in infarcted hearts were shown to correspond well with noninfarcted and infarcted regions as detected by delayed enhancement cardiovascular magnetic resonance images.

Electrophysiological evaluation of sensory and motor pathways after incomplete unilateral spinal cord contusion.

OBJECT Unilateral contusions represent an increasingly popular model for studying the pathways and recovery mechanisms of spinal cord injury (SCI). Current studies rely heavily on motor behavior scoring and histological evidence to make assessments. Electrophysiology represents one way to reliably quantify the functionality of motor pathways. The authors sought to quantify the functional integrity of the bilateral motor and sensory pathways following unilateral SCI by using measurements of motor and somatosensory evoked potentials (MEPs and SSEPs, respectively). METHODS Eighteen rats were randomly divided into 3 groups receiving a mild unilateral contusion, a mild midline contusion, or a laminectomy only (control). Contusions were induced at T-8 using a MASCIS impactor. Electrophysiological analysis, motor behavior scoring, and histological quantifications were then performed to identify relationships among pathway conductivity, motor function, and tissue preservation. RESULTS Hindlimb MEPs ipsilateral to the injury showed recovery by Day 28 after injury and corresponded to approximately 61% of spared corticospinal tract (CST) tissue. In contrast, MEPs of the midline-injured group did not recover, and correspondingly > 90% of the CST tissue was damaged. Somatosensory evoked potentials showed only a moderate reduction in amplitude, with no difference in latency for the pathways ipsilateral to injury. Furthermore, these SSEPs were significantly better than those of the midline-injured rats for the same amount of white matter damage. CONCLUSIONS Motor evoked potential recovery corresponded to the amount of spared CST in unilateral and midline injuries, but motor behavior consistently recovered independent of MEPs. These data support the idea that spared contralateral pathways aid in reducing the functional deficits of injured ipsilateral pathways and further support the idea of CNS plasticity.

Cardiac motion estimation by joint alignment of tagged MRI sequences.

Image registration has been proposed as an automatic method for recovering cardiac displacement fields from tagged Magnetic Resonance Imaging (tMRI) sequences. Initially performed as a set of pairwise registrations, these techniques have evolved to the use of 3D+t deformation models, requiring metrics of joint image alignment (JA). However, only linear combinations of cost functions defined with respect to the first frame have been used. In this paper, we have applied k-Nearest Neighbors Graphs (kNNG) estimators of the α-entropy (H(α)) to measure the joint similarity between frames, and to combine the information provided by different cardiac views in an unified metric. Experiments performed on six subjects showed a significantly higher accuracy (p<0.05) with respect to a standard pairwise alignment (PA) approach in terms of mean positional error and variance with respect to manually placed landmarks. The developed method was used to study strains in patients with myocardial infarction, showing a consistency between strain, infarction location, and coronary occlusion. This paper also presents an interesting clinical application of graph-based metric estimators, showing their value for solving practical problems found in medical imaging.

Comprehensive use of cardiac computed tomography to guide left ventricular lead placement in cardiac resynchronization therapy

Background Optimal lead positioning is an important determinant of cardiac resynchronization therapy (CRT) response. Objective The purpose of this study was to evaluate cardiac computed tomography (CT) selection of the optimal epicardial vein for left ventricular (LV) lead placement by targeting regions of late mechanical activation and avoiding myocardial scar. Methods Eighteen patients undergoing CRT upgrade with existing pacing systems underwent preimplant electrocardiogram-gated cardiac CT to assess wall thickness, hypoperfusion, late mechanical activation, and regions of myocardial scar by the derivation of the stretch quantifier for endocardial engraved zones (SQUEEZ) algorithm. Cardiac venous anatomy was mapped to individualized American Heart Association (AHA) bull’s-eye plots to identify the optimal venous target and compared with acute hemodynamic response (AHR) in each coronary venous target using an LV pressure wire. Results Fifteen data sets were evaluable. CT-SQUEEZ–derived targets produced a similar mean AHR compared with the best achievable AHR (20.4% ± 13.7% vs 24.9% ± 11.1%; P = .36). SQUEEZ-derived guidance produced a positive AHR in 92% of target segments, and pacing in a CT-SQUEEZ target vein produced a greater clinical response rate vs nontarget segments (90% vs 60%). Conclusion Preprocedural CT-SQUEEZ–derived target selection may be a valuable tool to predict the optimal venous site for LV lead placement in patients undergoing CRT upgrade.

Low-dose lung cancer screening with photon-counting CT: a feasibility study

To evaluate the feasibility of using a whole-body photon-counting detector (PCD) CT scanner for low-dose lung cancer screening compared to a conventional energy integrating detector (EID) system. Radiation dose-matched EID and PCD scans of the COPDGene 2 phantom were acquired at different radiation dose levels (CTDIvol: 3.0, 1.5, and 0.75 mGy) and different tube voltages (120, 100, and 80 kVp). EID and PCD images were compared for quantitative Hounsfield unit (HU) accuracy, noise levels, and contrast-to-noise ratios (CNR) for detection of ground-glass nodules (GGN) and emphysema. The PCD HU accuracy was better than EID for water at all scan parameters. PCD HU stability for lung, GGN and emphysema regions were superior to EID and PCD attenuation values were more reproducible than EID for all scan parameters (all P  <  0.01), while HUs for lung, GGN and emphysema ROIs changed significantly for EID with decreasing dose (all P  <  0.001). PCD showed lower noise levels at the lowest dose setting at 120, 100 and 80 kVp (15.2  ±  0.3 HU versus 15.8  ±  0.2 HU, P  =  0.03; 16.1  ±  0.3 HU versus 18.0  ±  0.4 HU, P  =  0.003; and 16.1  ±  0.3 HU versus 17.9  ±  0.3 HU, P  =  0.001, respectively), resulting in superior CNR for evaluation of GGNs and emphysema at 100 and 80 kVp. PCD provided better HU stability for lung, ground-glass, and emphysema-equivalent foams at lower radiation dose settings with better reproducibility than EID. Additionally, PCD showed up to 10% less noise, and 11% higher CNR at 0.75 mGy for both 100 and 80 kVp. PCD technology may help reduce radiation exposure in lung cancer screening while maintaining diagnostic quality.

Photon‐counting CT for simultaneous imaging of multiple contrast agents in the abdomen: An in vivo study

Purpose: To demonstrate the feasibility of spectral imaging using photon‐counting detector (PCD) x‐ray computed tomography (CT) for simultaneous material decomposition of three contrast agents in vivo in a large animal model. Methods: This Institutional Animal Care and Use Committee‐approved study used a canine model. Bismuth subsalicylate was administered orally 24–72 h before imaging. PCD CT was performed during intravenous administration of 40–60 ml gadoterate meglumine; 3.5 min later, iopamidol 370 was injected intravenously. Renal PCD CT images were acquired every 2 s for 5–6 min to capture the wash‐in and wash‐out kinetics of the contrast agents. Least mean squares linear material decomposition was used to calculate the concentrations of contrast agents in the aorta, renal cortex, renal medulla and renal pelvis. Results: Using reference vials with known concentrations of materials, we computed molar concentrations of the various contrast agents during each phase of CT scanning. Material concentration maps allowed simultaneous quantification of both arterial and delayed renal enhancement in a single CT acquisition. The accuracy of the material decomposition algorithm in a test phantom was −0.4 ± 2.2 mM, 0.3 ± 2.2 mM for iodine and gadolinium solutions, respectively. Peak contrast concentration of gadolinium and iodine in the aorta, renal cortex, and renal medulla were observed 16, 24, and 60 s after the start each injection, respectively. Conclusion: Photon‐counting spectral CT allowed simultaneous material decomposition of multiple contrast agents in vivo. Besides defining contrast agent concentrations, tissue enhancement at multiple phases was observed in a single CT acquisition, potentially obviating the need for multiphase CT scans and thus reducing radiation dose.

Dual-contrast agent photon-counting computed tomography of the heart: initial experience

To determine the feasibility of dual—contrast agent imaging of the heart using photon-counting detector (PCD) computed tomography (CT) to simultaneously assess both first-pass and late enhancement of the myocardium. An occlusion-reperfusion canine model of myocardial infarction was used. Gadolinium-based contrast was injected 10 min prior to PCD CT. Iodinated contrast was infused immediately prior to PCD CT, thus capturing late gadolinium enhancement as well as first-pass iodine enhancement. Gadolinium and iodine maps were calculated using a linear material decomposition technique and compared to single-energy (conventional) images. PCD images were compared to in vivo and ex vivo magnetic resonance imaging (MRI) and histology. For infarct versus remote myocardium, contrast-to-noise ratio (CNR) was maximal on late enhancement gadolinium maps (CNR 9.0 ± 0.8, 6.6 ± 0.7, and 0.4 ± 0.4, p < 0.001 for gadolinium maps, single-energy images, and iodine maps, respectively). For infarct versus blood pool, CNR was maximum for iodine maps (CNR 11.8 ± 1.3, 3.8 ± 1.0, and 1.3 ± 0.4, p < 0.001 for iodine maps, gadolinium maps, and single-energy images, respectively). Combined first-pass iodine and late gadolinium maps allowed quantitative separation of blood pool, scar, and remote myocardium. MRI and histology analysis confirmed accurate PCD CT delineation of scar. Simultaneous multi-contrast agent cardiac imaging is feasible with photon-counting detector CT. These initial proof-of-concept results may provide incentives to develop new k-edge contrast agents, to investigate possible interactions between multiple simultaneously administered contrast agents, and to ultimately bring them to clinical practice.

Reconstruction of difference in sequential CT studies using penalized likelihood estimation

Characterization of anatomical change and other differences is important in sequential computed tomography (CT) imaging, where a high-fidelity patient-specific prior image is typically present, but is not used, in the reconstruction of subsequent anatomical states. Here, we introduce a penalized likelihood (PL) method called reconstruction of difference (RoD) to directly reconstruct a difference image volume using both the current projection data and the (unregistered) prior image integrated into the forward model for the measurement data. The algorithm utilizes an alternating minimization to find both the registration and reconstruction estimates. This formulation allows direct control over the image properties of the difference image, permitting regularization strategies that inhibit noise and structural differences due to inconsistencies between the prior image and the current data. Additionally, if the change is known to be local, RoD allows local acquisition and reconstruction, as opposed to traditional model-based approaches that require a full support field of view (or other modifications). We compared the performance of RoD to a standard PL algorithm, in simulation studies and using test-bench cone-beam CT data. The performances of local and global RoD approaches were similar, with local RoD providing a significant computational speedup. In comparison across a range of data with differing fidelity, the local RoD approach consistently showed lower error (with respect to a truth image) than PL in both noisy data and sparsely sampled projection scenarios. In a study of the prior image registration performance of RoD, a clinically reasonable capture ranges were demonstrated. Lastly, the registration algorithm had a broad capture range and the error for reconstruction of CT data was 35% and 20% less than filtered back-projection for RoD and PL, respectively. The RoD has potential for delivering high-quality difference images in a range of sequential clinical scenarios including image-guided surgeries and treatments where accurate and quantitative assessments of anatomical change is desired.