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This study was aimed to detect the effects of gambogic acid (GA) on the growth of chronic myelogenous leukemia (CML) K562 cells. Our results showed that GA induced the accumulation of autophagic vacuoles and up-regulation of two autophagy-related proteins (Beclin 1 and LC3). GA also induced down-regulation of mRNA levels of BCR-ABL fusion gene and SQSTM1/sequestosome 1 (p62) protein levels. After treatment by chloroquine (CQ) and pan caspase inhibitor Z-VAD-FMK (PC), both GA-induced autophagy and apoptosis were inhibited. Our study demonstrates that GA may induce cell death through autophagy and apoptosis pathways in CML K562 cells. A cross-talk mechanism exists between GA-induced autophagy and apoptosis. However, the mechanism of GA for inducing autophagy and apoptosis need further clarification. more...

We propose an experimental method to investigate the dominant multiple node charge collection mechanism. A transistor array-based test structure is used to distinguish charge collection owing to the drift-diffusion and parasitic bipolar amplification effect. Heavy ion experimental results confirm that drift-diffusion dominates multiple node charge collection at low linear energy transfer (LET). However, the parasitic bipolar amplification effect dominates it at high LET. We also propose simple equations to determine the critical LET which may change the dominant multiple node charge collection mechanism. The calculated LET value is consistent with the heavy ion experimental results. more...

Multiple lines of evidence have demonstrated that increased expression of phospholipid scramblase 1 (PLSCR1) is involved in the differentiation of acute myeloid leukemia (AML) cells by several differentiation-inducing agents including ATRA and phorbol 12-myristate 13-acetate. However, none of these agents can achieve nonhomogenous subcellular distribution of PLSCR1. We have demonstrated that wogonoside possesses differentiation and anti-leukemic effects in AML cell lines by promoting PLSCR1 trafficking into nucleus. Here we report that wogonoside promotes the expression of PLSCR1 and enhances its nuclear translocation and binding to the 1, 4, 5-trisphosphate receptor 1 (IP3R1) promoter in AML patient-derived primary cells. Wogonoside activates IP3R1, in turn, promotes release of Ca2+ from endoplasmic reticulum, and eventually leads to cell differentiation. Our in vivo study further confirms that wogonoside can promote PLSCR1 and IP3R1 expression in primary AML cells and reduce the AML cell counts in engrafted nonobese diabetic/severe combined immunodeficient mice. Taken together, our findings provide new insight into the mechanism of wogonoside-induced differentiation and anti-leukemic effect on primary AML cells, suggesting the therapeutic potential of wogonoside for AML, especially for non-APL AML. more...

The current work was based on a previously developed 4D image reconstruction method for myocardial perfusion (MP) PET where dual respiratory motion (RM) and cardiac motion (CM) compensation were performed post reconstruction. We implemented and extended the work on patient data from a commercial PET system and demonstrated further image quality improvement. We divided the PET events into 6 equal-count respiratory gates based on heart “center-of-mass” movement estimated from the list-mode PET data. For each respiratory gate, the list-mode data was sorted and rebinned into 8 and 16 cardiac gates in addition to the conventional 8 cardiac gates. The vendor provided list-mode based time-of-flight reconstruction was used in all image reconstruction with and without the TOF information to provide high quality 3D PET images before the RMC the CM compensated image at each cardiac gate was the sum of the original image and images transformed from the other cardiac gates based on the CMVF. Dual RM&CM compensation were shown to improve spatial resolution by reducing RM blur through RM compensation and suppressing image noise through CM compensation as compared to those without CM compensation. The 16-frame cardiac gated images provided much higher temporal resolution for revealing subtle regional motion than the 8-frame cardiac gated images and showed similar noise level per frame. In conclusion, dual RM&CM compensation improves spatial resolution and allows higher number of cardiac gated frames in 4D gated MP PET with improved temporal resolution without compromise in image noise. more...

Although the very first computed tomographic scanners used the iterative algebraic reconstruction technique, the filtered back-projection (FBP) method soon became the gold standard for computed tomographic reconstruction. Image quality has dramatically improved over the past 30 years thanks to advances in x-ray tubes, detector technologies, and overall system design and integration, as well as refinements to image reconstruction algorithms. Typical effective dose values range from 5 to 7 mSv for chest computed tomography (CT) and from 8 to 12 mSv for abdominal and pelvic CT, compared with 0.02 to 0.2 mSv for chest x-ray, making CT a comparatively high-dose modality. Nearly 68.7 million CT procedures were performed in the United States in 2007 [1]. The number of CT procedures has been increasing dramatically in the United States, by nearly 10% annually, since the commercial introduction of multirow detector CT scanners. Because of this significant increase in the use of CT, there is concern about radiation exposure to the population. Methods to reduce radiation dose and at the same time retain comparable image quality are being actively pursued both in academia and in the industry. In the past decade, thanks to increasing computational power, statistical iterative reconstruction (IR) has become a hot research topic in CT, with a focus on noise suppression, artifact reduction, and dual-energy or energy-sensitive imaging. Some of these efforts are now under translation from bench to bedside. more...

The goal of this conference record is to present the experiments conducted to evaluate a magnetic resonance (MR) compatible, simultaneous SPECT-MR insert for small animal (SA) imaging that we have been working on for the last three years. As previously demonstrated, the insert consists of 5 rings of 19 MR compatible CZT detectors connected seamlessly. A multi-pinhole (MPH) collimator with focused pinholes was built using a plastic shell filled with high-density coated tungsten powder and fitted with solid tungsten pinhole inserts. To acquire SPECT and MR data simultaneously, a shielded transmit/receive radio frequency (RF) coil is inserted into the MPH collimator. The insert was evaluated as a standalone SA SPECT system using both a hot-rod resolution phantom (HR-RP) experiment and SA imaging studies. Furthermore, simultaneous SPECT-MR phantom and SA imaging experiments were conducted by placing the SPECT-MR insert inside a 3T clinical MRI system. From acquired experimental data, SPECT images were reconstructed using an in-house developed 3D MPH ML-EM method with pinhole collimator detector response model and compensation. As a standalone SA SPECT system, the insert provided good quality images in phantom and SA studies. The quality of the SPECT images of the HR-RP acquired during the simultaneous SPECT-MR imaging experiment was comparable to the quality of the images acquired during standalone SPECT acquisition. Despite the fact that the SPECT insert degraded the MR image signal-to-noise-ratio (SNR) and caused field distortions, MR imaging was possible within the specific field-of-view of interest. When registered and fused, the SPECT and MR HR-RP images were found to be in acceptable geometric agreement. Data acquired during the simultaneous SPECT-MR SA study was used to obtain a dynamic SPECT image and Time Activity Curve showing initial uptake and later washout of 99mTc MAG3 into and out of a mouse's kidneys. Furthermore, a SPECT kidney image was fused with the simultaneously acquired MR image and showed acceptable geometric agreement. Fast dynamic MR imaging was not possible due to severe geometric distortions present when using high speed sequences. These experimental results demonstrate the ability of the insert to obtain SA SPECT dynamic studies and the feasibility of simultaneous SA SPECT-MR imaging. Further engineering improvements remain to be explored to reduce the interaction between the SPECT and MR systems and to eventually enable simultaneous fast dynamic MR studies over the full volume of subject animals. more...

This work is a continuation of our previous work on geometric calibration in the circular cone-beam geometry. It is well known that seven parameters completely describe such a geometry in either flat-panel X-ray computed tomography or single pinhole SPECT imaging. Previously we developed a graphical procedure to determine the detector in-plane rotation angle independently of the other six parameters. Using the discovered geometrical relationships, in this paper we determine the remaining six parameters using the cone-beam projections of a minimum of three point objects. Our method is analytical. It makes use of the parameters of the fitted ellipse from the calibration data. The parameter estimation is accurate in the noise-free case or when there is moderate projection data truncation or shorter calibration scan range ( ≤ 360°). We perform numerical evaluations to study the robustness of the proposed method under different projection noise levels and using different data acquisition ranges. Using a full 360° scan range, the estimation accuracy and precision of our method are comparable or superior to previous methods. Using a shorter acquisition range, there may be bias in the ellipse parameters obtained by simple algebraic fitting methods. This bias will propagate to the estimated geometric parameters. Such bias can be mostly eliminated by using a more sophisticated fitting algorithm. At the same noise level, the geometric parameter estimation accuracies are comparable, but the estimation precision degrades, as the acquisition range becomes shorter. more...

To study the mechanisms in gambogic acid (GA) -induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro.The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection. Apoptosis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3, -8 and -9 were detected by colorimetric assay. Bcl-2 and Bax were analyzed by Western blotting.GA inhibited cell growth in a time- and dose- dependent manner. GA induces apoptosis in JeKo-1 cells but not in normal bone marrow cells, which was involved in reducing the membrane potential of mitochondria, activating caspases-3, -8 and -9 and decreasing the ratio of Bcl-2 and Bax without cell cycle arresting.GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3, -8 and -9 via mitochondrial pathway without affecting cell cycle. more...

Objective: To increase the knowledge and experience of treating left-sided endocarditis patients complicated with hemophagocytic lymphohistiocytosis. Method: One case with left-sided endocarditis and secondary hemophagocytic lymphohistiocytosis was reported and related PubMed literatures were reviewed. Results: A 40-year-old Asian female came to hospital with uncontrolled repeated fever that had lasted for more than one month. Prior to this admission, the patient suffered a sub-acute liver failure of unknown cause and received artificial liver support and intravenous hepatic protectants in the local hospital, and the patient responded well. At that time echocardiography revealed congenital heart disease. After admission to our hospital, her lab results showed pancytopenia, coagulation abnormal and significantly elevated levels of total bilirubin, soluble CD25 and serum ferritin. Bone marrow biopsy was negative for hemaphagocytosis. The full body PET-CT was performed and the results demonstrated hepato-splenomegaly and relatively increased standard uptake value (SUV) of the spleen, with no signs of malignancies. Several sets of blood cultures were all positive for methicillin-resistant Staphylococcus epidermidis (MRSE). Two weeks later, cardiac ultrasound images were obtained and showed a completely well-shaped vegetation attached to the aorta valve, which confirmed the diagnosis of definite infectious endocarditis (IE). So the final diagnosis was the MRSE-related left-sited infectious endocarditis and acquired HLH. The Multi-disciplinary team (MDT) discussed this critical case, since the allergic reaction of vancomycin and no therapeutic effect of tecolplanin for 10 days, the patient was treated by high dose daptomycin(10 mg/kg once daily) and chemotherapy according to HLH-2004 protocol, afterwards the patient's condition was improved, cardiothoracic surgery was performed smoothly and the vegetation on the aortic valve was successfully removed. Till now the patient has been in good condition for more than 2 years. There are only 4 case reports pertinent to endocarditis with HLH published in PubMed and these related cases were also reviewed. Conclusion: This case report is the description of another rare and complicated condition in which the patient concurrently developed left-sided infectious endocarditis and acquired HLH. High dose daptomycin monotherapy was effective for controlling MRSE-related left-sided IE. Early diagnosis and intervention is very important for the successful treatment of HLH. Our case also highlights the importance of the multi-disciplinary team (MDT) model in dealing with similar critical cases in the clinic work. Disclosures No relevant conflicts of interest to declare. more...

GL-V9, a newly synthetic flavonoid derivative, is an active cytotoxic component and exhibits anticancer activities. Here, we demonstrated the sequence of death reponses to different concentration of GL-V9 in human T-cell malignancies cell Jurkat and HuT78. Responses included transient accumulation of cells at the G2/M border followed by also transient rise in several mitotic markers and mitotic attempts were largely abnormal, resulting in numerous micronucleated and multinucleated cells in low drug concentration (2 μM), as shown by flow cytometre analyses and Giemsa staining. These events, indicative of mitotic catastrophe, were not associated with immediate cell death. However, MTT assay showed that high concentration of GL-V9 (4, 8, 16 μM) causes near complete cell growth inhibition at 12 h. Also, the classical manifestations of apoptosis (including phosphatidylserine externalization, mitochondrial dysfunction, and caspase activation) were marginal at 24 h, as shown by Annexin V-PI staining, JC-1, and western blot assay. The mechanism research reveals that low dose of GL-V9 induced mitotic catastrophe via decreasing EEA1, which is required for cytokinesis, and increasing the expression of PTEN. Besides, high concentration of GL-V9 induced cell apoptosis by up-regulating the expression of apoptosis-related proteins caspase 3 and Bim in lymphoid tumor cell lines and primary ALL cells. Collectively, these findings show that different concentrations of GL-V9 can induce mitotic catastrophe and ultimate cell death event of human T-cell malignancies respectively, which would be a potential therapeutical compound for treating human lymphoid tumor. Disclosures No relevant conflicts of interest to declare. more...

Purpose: To develop a feature-preserving model based image reconstruction (MBIR) method that improves performance in pancreatic lesion classification at equal or reduced radiation dose. Methods: A set of pancreatic lesion models was created with both benign and premalignant lesion types. These two classes of lesions are distinguished by their fine internal structures; their delineation is therefore crucial to the task of pancreatic lesion classification. To reduce image noise while preserving the features of the lesions, we developed a MBIR method with curvature-based regularization. The novel regularization encourages formation of smooth surfaces that model both the exterior shape and the internal features of pancreatic lesions. Given that the curvature depends on the unknown image, image reconstruction or denoising becomes a non-convex optimization problem; to address this issue an iterative-reweighting scheme was used to calculate and update the curvature using the image from the previous iteration. Evaluation was carried out with insertion of the lesion models into the pancreas of a patient CT image. Results: Visual inspection was used to compare conventional TV regularization with our curvature-based regularization. Several penalty-strengths were considered for TV regularization, all of which resulted in erasing portions of the septation (thin partition) in a premalignant lesion. At matched noise variance (50% noise reduction in the patient stomach region), the connectivity of the septation was well preserved using the proposed curvature-based method. Conclusion: The curvature-based regularization is able to reduce image noise while simultaneously preserving the lesion features. This method could potentially improve task performance for pancreatic lesion classification at equal or reduced radiation dose. The result is of high significance for longitudinal surveillance studies of patients with pancreatic cysts, which may develop into pancreatic cancer. The Senior Author receives financial support from Siemens GmbH Healthcare more...

We present a stored system matrix (SM) approach for iterative x-ray CT image reconstruction with helical cone-beam geometry. Because of the symmetry of a helical source trajectory, it is sufficient to calculate and store the SM entries for one transaxial slice only and for all source positions illuminating the slice. This is made possible by (1) selecting the reconstruction slice thickness to be an integer multiple of the source translation per projection view, and (2) discretizing the 3D reconstruction volume on a rotated stack of slices. Using the proposed method, the memory requirement for reconstructing a full field-of-view of clinical scanners is manageable on current computing platforms. The same storage principle can be generalized and applied to volume-of-interest (VOI) image reconstruction for helical cone-beam CT. In this case, the stored SM entries correspond to a partial- or full-ring region on one transaxial slice, and for all source positions illuminating the ring. The size and location of the ring depend on the size and the location of the VOI and the scan geometry. We demonstrate by both computer simulations and clinical patient data the speed and efficacy of iterative image reconstruction using the stored SM approach. more...

Autologous hematopoietic stem cell transplantation (AHSCT) has the potential to induce clinical remission in patients with newly diagnosed type 1 diabetes.The objective of the study was to examine the impact of AHSCT on lymphocytes and pancreatic β-cell function.This was a nonrandomized, open-label prospective study.Thirteen patients with new onset of type 1 diabetes, 10 of them with diabetic ketoacidosis, were subjected to AHSCT with cryopreserved CD34(+) progenitor cells and followed up for 31-54 months.The numbers of different subsets of lymphocytes and the levels of serum cytokines, islet antibodies, C-peptide, and plasma glycosylated hemoglobin were longitudinally measured.The numbers of different subsets of lymphocytes, except for CD8(+) T cells, in the patients before AHSCT were significantly lower than those in controls. However, all lymphocytes gradually recovered after AHSCT, accompanied by decreased levels of serum autoantibodies, IL-1, IL-17, and TNF-α. After AHSCT, 11 of 13 patients required significantly reduced doses of insulin for adequate glycemic control, accompanied by reduced levels of glycosylated hemoglobin but increased C-peptide concentrations. Three patients achieved exogenous insulin independence for 7-54 months. The survival of remaining β-cells was associated positively with the preexisting β-cell function but negatively with preexisting autoantibodies (P0.05). The numbers of infused CD34(+) cells were positively correlated with the concentrations of serum IL-10, IL-4, TGF-β, and fasting C-peptide but negatively correlated with the levels of serum TNF-α and insulin doses after AHSCT (P0.05).AHSCT modulated lymphocytes and preserved β-cell function in Chinese patients with new onset of type 1 diabetes and diabetic ketoacidosis. more...

It is well known that seven parameters completely describe a circular cone-beam geometry in either flat-panel X-ray computed tomography (CT) or single pinhole SPECT imaging. This paper considers the problem of determining one of the seven parameters only, the detector in-plane rotation or twist angle η. We describe a graphical procedure that can determine η independently of all other six parameters from a geometric calibration scan of point objects. Our method is exact in the ideal noise-free case and is general in that the other two out-of-plane detector rotation angles θ and φ can be nonzero. The calibration scan typically needs at least two point objects and an even number of projection views over a full 360° data acquisition. Under certain conditions, projection data truncation or a short scan acquisition of 180° + fan angle can be accommodated without affecting the accuracy of the calibration result. The graphical method is equally applicable to rotational multipinhole SPECT geometry. In this case, the final result is averaged from the individual estimates considering each pinhole separately. We use computer simulations and a multipinhole SPECT experiment to demonstrate the accuracy and precision of the proposed method. more...

The purpose of the study was to systematically design two multipinhole (MPH) collimators for a MR compatible seamless small animal SPECT detector ring (DR) that, for a given system resolution (SR), maximized detector area usage and achieved highest possible geometric efficiency (GE) within the system's design constraints. The SPECT DR consists of 5 rings of 19 2.56×2.56cm2 individual CZT detectors connected seamlessly with a total area of 62,259mm2. A set of multipinhole apertures was arranged on a cylindrical collimator sleeve (CS) and had a common-volume-of-view (CVOV) of 50mm diameter. more...

Our goal is to develop a high performance SPECT system for simultaneous SPECT-MR imaging of small animals (SA). The SPECT system has inner diameter (ID) of 15.4 cm and outer diameter of 19.8 cm. It comprises five seamless cylindrical detectors, each with 19 CZT modules (2.54×2.54 cm2, 16×16 pixels). The SPECT system can be operated either stand-alone or as an insert into an MRI system with a minimum 20 cm bore. Cylindrical multipinhole (MPH) collimator sleeves (CSs), made with tungsten powder and solid tungsten pinhole apertures, were designed to provide maximum geometric efficiency under the system's geometric constraints. Different MPH collimators were designed for mouse or rat imaging, and for static high-resolution or dynamic imaging without CS rotation. Sparse-view image reconstruction methods reduce CS rotation. Monte Carlo simulations confirm the SPECT imaging characteristics of 2 MPH CSs that have 18 and 36 pinholes with 1 mm and 1.5 mm system resolution, respectively. Sparse-view 3D MPH image reconstruction with system response modeling indicates that 36 pinholes are sufficient to provide artifact-free images at 1.5 mm resolution without CS rotation. The SPECT system with the 2 MPH CSs, the RF coil, and all mechanical and electronics components have been constructed. Initial experimental phantom and small animal studies demonstrated the high performance and imaging characteristics of the SPECT system. In conclusion, a high performance small animal (SA) SPECT system has been designed and constructed for simultaneous SA SPECT-MRI. Initial subsystem testing has demonstrated excellent SPECT and MRI imaging performance that matches design predictions. more...

The goal was to evaluate different acquisition strategies (AS) of a dual-head (DH) Rotating 4-Segment Slant-Hole (R4SSH) SPECT system for improved myocardial perfusion (MP) SPECT imaging.

Autologous haematopoietic stem cell transplantation (AHSCT) is a promising treatment for multiple sclerosis (MS) patients who have not adequately responded to conventional therapies. We retrospectively evaluated the safety and long-term clinical outcome of AHSCT in MS patients in China. Twenty-five patients with various types of MS were treated with AHSCT. Peripheral blood stem cells were derived by leukapheresis after mobilized with granulocyte colony-stimulating factor. Then CD34+ cell selection of the graft was performed and anti-thymocyte globulin was given for T-cell depletion, with the conditioning regimen BEAM adopted and early and late toxicities recorded. Long-term responses were evaluated by the expanded disability status scale (EDSS), progression-free survival and gadolinium-enhanced magnetic resonance imaging scans. 10, 7 and 8 patients experienced neurological improvement, stabilization and progression, respectively. The median EDSS scores observed over 1-year follow-up after transplantation (5.5–7.0) were consistently lower than the baseline (8.0). The progression-free survival rate was 74, 65 and 48% at 3, 6 and 9 years post-transplant. 58% cases (7/12) had active lesions at baseline and all turned to inactive status in the years of follow-up. 25% cases (3/12) experienced progression after transplantation but had no active lesions in MRI over the whole follow-up period. 17% cases (2/12) without active lesions at baseline progressed active lesions in MRI. The major early toxicity resulted in fever and late toxicity caused transplantation-related mortality due to severe pneumonia and varicella-zoster virus hepatitis, respectively. AHSCT is a feasible treatment for severe MS and its long-term efficacy is favorable. more...

We present an efficient scheme for the forward and backward projector implementation for helical cone-beam x-ray CT reconstruction using a pre-calculated and stored system matrix approach. Because of the symmetry of a helical source trajectory, it is sufficient to calculate and store the system matrix entries for one image slice only and for all source positions illuminating it. The system matrix entries for other image slices are copies of those stored values. In implementing an iterative image reconstruction method, the internal 3D image volume can be based on a non-Cartesian grid so that no system matrix interpolation is needed for the repeated forward and backward projection calculation. Using the proposed scheme, the memory requirement for the reconstruction of a full field-of-view of clinical scanners is manageable on current computing platforms. The same storage principle can be generalized and applied to iterative volume-of-interest image reconstruction for helical cone-beam CT. We demonstrate by both computer simulations and clinical patient data the speed and image quality of VOI image reconstruction using the proposed stored system matrix approach. We believe the proposed method may contribute to bringing iterative reconstruction to the clinical practice. more...

We describe a continuing design and development of MR-compatible SPECT systems for simultaneous SPECT-MR imaging of small animals. A first generation prototype SPECT system was designed and constructed to fit inside a MRI system with a gradient bore inner diameter of 12 cm. It consists of 3 angularly offset rings of 8 detectors (1"x1", 16x16 pixels MR-compatible solid-state CZT). A matching 24-pinhole collimator sleeve, made of a tungsten-compound, provides projections from a common FOV of ~25 mm. A birdcage RF coil for MRI data acquisition surrounds the collimator. The SPECT system was tested inside a clinical 3T MRI system. Minimal interference was observed on the simultaneously acquired SPECT and MR images. We developed a sparse-view image reconstruction method based on accurate modeling of the point response function (PRF) of each of the 24 pinholes to provide artifact-free SPECT images. The stationary SPECT system provides relatively low resolution of 3-5 mm but high geometric efficiency of 0.5- 1.2% for fast dynamic acquisition, demonstrated in a SPECT renal kinetics study using Tc-99m DTPA. Based on these results, a second generation prototype MR-compatible SPECT system with an outer diameter of 20 cm that fits inside a mid-sized preclinical MRI system is being developed. It consists of 5 rings of 19 CZT detectors. The larger ring diameter allows the use of optimized multi-pinhole collimator designs, such as high system resolution up to ~1 mm, high geometric efficiency, or lower system resolution without collimator rotation. The anticipated performance of the new system is supported by simulation data. more...

The goal of the study was to investigate data acquisition strategies and image reconstruction methods for a stationary SPECT insert that can operate inside an MRI scanner with a 12 cm bore diameter for simultaneous SPECT/MRI imaging of small animals. The SPECT insert consists of 3 octagonal rings of 8 MR-compatible CZT detectors per ring surrounding a multi-pinhole (MPH) collimator sleeve. Each pinhole is constructed to project the field-of-view (FOV) to one CZT detector. All 24 pinholes are focused to a cylindrical FOV of 25 mm in diameter and 34 mm in length. The data acquisition strategies we evaluated were optional collimator rotations to improve tomographic sampling; and the image reconstruction methods were iterative ML-EM with and without compensation for the geometric response function (GRF) of the MPH collimator. For this purpose, we developed an analytic simulator that calculates the system matrix with the GRF models of the MPH collimator. The simulator was used to generate projection data of a digital rod phantom with pinhole aperture sizes of 1 mm and 2 mm and with different collimator rotation patterns. Iterative ML-EM reconstruction with and without GRF compensation were used to reconstruct the projection data from the central ring of 8 detectors only, and from all 24 detectors. Our results indicated that without GRF compensation and at the default design of 24 projection views, the reconstructed images had significant artifacts. Accurate GRF compensation substantially improved the reconstructed image resolution and reduced image artifacts. With accurate GRF compensation, useful reconstructed images can be obtained using 24 projection views only. This last finding potentially enables dynamic SPECT (and/or MRI) studies in small animals, one of many possible application areas of the SPECT/MRI system. Further research efforts are warranted including experimentally measuring the system matrix for improved geometrical accuracy, incorporating the co-registered MRI image in SPECT reconstruction, and exploring potential applications of the simultaneous SPECT/MRI SA system including dynamic SPECT studies. more...

Molecular analyses such as fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are demanded to improve diagnostic accuracy in addition to immunohistopathology of bone marrow (BM) trephine specimens. Conventional BM embedding method needs decalcification, and its procedure may impair tissue morphology and DNA quality. Here, we report an undecalcified method by which glycol methacrylate resin is polymerized at low temperature (4°C). Using this method, BM enzyme activity and antigenic determinants are well preserved, and moreover, DNA extracted from plastic embedding sections is suitable for PCR amplification and sequencing, FISH analysis can be well done because of the DNA integrity of BM sections. If working with BM trephine specimen, our protocol offers the possibility to combine superior morphology with modern molecular analysis. more...

We describe a single photon emission computed tomograph (SPECT) which can be operated inside state-of-the-art magnetic resonance imaging (MRI) systems. The combined SPECT/MRI system allows one to acquire simultaneously the data from both modalities and co-register the images in space and time. The new SPECT is based on the semiconductor cadmium zinc telluride (CZT) and application specific integrated circuits (ASICs) — two technologies which are MR-compatible and almost insensitive to magnetic fields. The SPECT camera has an energy resolution of 5.4 keV full-width-half-maximum (FWHM) at the 140-keV photo peak from 99mTc for either inside or outside of the MRI. We acquired the first SPECT and MR images from resolution phantoms and mice in-vivo. The experiments show that the MRI is minimally affected by the SPECT camera inside the bore. Preliminary results for the SPECT camera show high sensitivity of about 1.6% and a spatial resolution of 4 mm FWHM. more...

This work aims at discriminating between soft and calcified coronary artery plaques using microCT with a multi-energywindow photon counting X-ray detector (PCXD). We have previously investigated a solid state X-ray detector which has the capability to count individual photons in different energy windows. The data from these energy windows may be treated as multiple simultaneous X-ray acquisitions within non-overlapping energy windows that can provide additional information about tissue differences. In this work, we simulated a photon counting detector with five energy windows. We investigated two approaches for using the energy information provided by this detector. First, we applied energy weighting to the reconstruction from different energy windows to improve the signal-to-noise ratio between calcified and soft plaques. This resulted in a significant improvement in the signal-to-noise ratio. Second, we applied the basis material decomposition method to discriminate coronary artery plaques based on their calcium content. The results were compared with those obtained using dual-kVp material decomposition. We observed significantly improved contrast-tonoise ratios for the PCXD-based approaches. more...

This work studies the dual formulation of a penalized maximum likelihood reconstruction problem in x-ray CT. The primal objective function is a Poisson log-likelihood combined with a weighted cross-entropy penalty term. The dual formulation of the primal optimization problem is then derived and the optimization procedure outlined. The dual formulation better exploits the structure of the problem, which translates to faster convergence of iterative reconstruction algorithms. A gradient descent algorithm is implemented for solving the dual problem and its performance is compared with the filtered back-projection algorithm, and with the primal formulation optimized by using surrogate functions. The 3D XCAT phantom and an analytical x-ray CT simulator are used to generate noise-free and noisy CT projection data set with monochromatic and polychromatic x-ray spectrums. The reconstructed images from the dual formulation delineate the internal structures at early iterations better than the primal formulation using surrogate functions. However the body contour is slower to converge in the dual than in the primal formulation. The dual formulation demonstrate better noise-resolution tradeoff near the internal organs than the primal formulation. Since the surrogate functions in general can provide a diagonal approximation of the Hessian matrix of the objective function, further convergence speed up may be achieved by deriving the surrogate function of the dual objective function. more...

We describe a single photon emission computed tomograph (SPECT) which can be operated inside state-of-theart magnetic resonance imaging (MRI) systems. The combined SPECT/MRI system allows one to acquire simultaneously the data from both modalities and co-register the images in space and time. Unlike conventional SPECT systems, which use scintillators and photomultiplier tubes, the new SPECT is based on the semiconductor cadmium zinc telluride (CZT) and application specific integrated circuits (ASICs) - two technologies which are MR-compatible and almost insensitive to magnetic fields. The γ-radiation imaging system has a 3-cm diameter fieldof- view and allows one to acquire regional tomographic images in mice without moving the camera. more...

This work applies a previously developed analytical algorithm to the reconstruction problem in a rotating multi-segment slant-hole (RMSSH) SPECT system. The RMSSH collimator has greater detection efficiency than the parallel-hole collimator with comparable spatial resolution at the expense of limited common volume-of-view (CVOV) and is therefore suitable for detecting low-contrast lesions in breast, cardiac and brain imaging. The absorption of gamma photons in both the human breast and brain can be assu- med to follow an exponential rule with a constant attenuation coefficient. In this work, the RMSSH SPECT data of a digital NCAT phantom with breast attachment are modeled as the uniformly attenuated Radon transform of the activity distribution. These data are reconstructed using an analytical algorithm called the DBH method, which is an acronym for the procedure of differentiation backprojection followed by a finite weighted inverse Hilbert transform. The projection data are first differentiated along a specific direction in the projection space and then backprojected to the image space. The result from this first step is equal to a one-dimensional finite weighted Hilbert transform of the object; this transform is then numerically inverted to obtain the reconstructed image. With the limited CVOV of the RMSSH collimator, the detector captures gamma photon emissions from the breast and from parts of the torso. The simulation results show that the DBH method is capable of exactly reconstructing the activity within a well-defined region-of-interest (ROI) within the breast if the activity is confined to the breast or if the activity outside the CVOV is uniformly attenuated for each measured projection, while a conventional filtered backprojection algorithm only reconstructs the high frequency components of the activity function in the same geometry. more...

Electronic noise compensation can be important for low-dose x-ray CT applications where severe photon starvation occurs. For clinical x-ray CT systems utilizing energy-integrating detectors, it has been shown that the detected x-ray intensity is compound Poisson distributed, instead of the Poisson distribution that is often studied in the literature. We model the electronic noise contaminated signal Z as the sum of a compound Poisson distributed random variable (r.v.) Y and a Gaussian distributed electronic noise N with known mean and variance. We formulate the iterative x-ray CT reconstruction problem with electronic noise compensation as a maximum-likelihood reconstruction problem. However the likelihood function of Z is not analytically trackable; instead of working with it directly, we formulate the problem in the expectation-maximization (EM) framework, and iteratively maximize the conditional expectation of the complete log-likelihood of Y . We further demonstrate that the conditional expectation of the surrogate function of the complete log-likelihood is a legitimate surrogate for the incomplete surrogate. Under certain linearity conditions on the surrogate function, a reconstruction algorithm with electronic noise compensation can be obtained by some modification of one previously derived without electronic noise considerations; the change incurred is simply replacing the unavailable, uncontaminated measurement Y by its conditional expectation E ( Y | Z ). The calculation of E ( Y | Z ) depends on the model of Y , N , and Z . We propose two methods for calculating this conditional expectation when Y follows a special compound Poisson distribution - the exponential dispersion model (ED). Our methods can be regarded as an extension of similar approaches using the Poisson model to the compound Poisson model. more...

Rotating multisegment slant-hole (RMSSH) single photon emission computed tomography (SPECT) is suitable for detecting small and low-contrast breast lesions since it has much higher detection efficiency than conventional SPECT with a parallel-hole collimator and can image the breast at a closer distance. Our RMSSH SPECT reconstruction extends a previous rotation-shear transformation-based method to include nonuniform attenuation and collimator-detector response (CDR) compensation. To evaluate our reconstruction method, we performed two phantom simulation studies with 1) an isolated breast and 2) a breast phantom attached to the body torso. The reconstructed RMSSH SPECT images with attenuation and CDR compensation showed improved quantitative accuracy and less image artifacts than without. To evaluate the clinical efficacy of RMSSH SPECT mammography, we used a simulation study to compare with planar scintimammography in terms of the signal-to-noise ratio (SNR) value of a breast lesion. The RMSSH SPECT reconstruction images showed higher SNR value than the planar scintimammography images and even more so as we applied compensation for attenuation and collimator detector response. We conclude that attenuation and CDR compensation provide RMSSH SPECT mammography images with improved quality and quantitative accuracy. more...

In this work we used a novel CdTe photon counting x-ray detector capable of very high count rates to perform x-ray micro-computed tomography (microCT). The detector had 2 rows of 384 square pixels each 1 mm in size. Charge signals from individual photons were integrated with a shaping time of ~60 ns and processed by an ASIC located in close proximity to the pixels. The ASIC had 5 energy thresholds with associated independent counters for each pixel. Due to the thresholding, it is possible to eliminate dark-current contributions to image noise. By subtracting counter outputs from adjacent thresholds, it is possible to obtain the number of x-ray photon counts in 5 adjacent energy windows. The detector is capable of readout times faster than 5 ms. A prototype bench-top specimen μCT scanner was assembled having distances from the tube to the object and detector of 11 cm and 82 cm, respectively. We used a conventional x-ray source to produce 80 kVp x-ray beams with tube currents up to 400 μA resulting in count rates on the order of 600 kcps per pixel at the detector. Both phantoms and a dead mouse were imaged using acquisition times of 1.8 s per view at 1° steps around the object. The count rate loss (CRL) characteristics of the detector were measured by varying the tube current and corrected for using a paralyzable model. Images were reconstructed using analytical fan-beam reconstruction. The reconstructed images showed good contrast and noise characteristics and those obtained from different energy windows demonstrated energy-dependent contrast, thus potentially allowing for material decomposition. more...

Emerging photon-counting detectors with energy discrimination ability for x-ray CT perform binning according to the energy of the incoming photons. Multiple output channels with different energy thresholds can be obtained in one irradiation. The energy dependency of attenuation coefficients can be described by a linear combination of basis functions, e.g., Compton scatter and photo-electric effect; their individual contributions can be differentiated by using the multiple energy channels hence material characterization is made possible. Conventional analytic approach is a two-step process. First decompose in the projection domain to obtain the sinograms corresponding to the coefficients of the basis functions, then apply FBP to obtain the individual material components. This two-step process may have poor quality and quantitative accuracy due to the lower counts in the separate energy channels and approximation errors propagated to the image domain from projection domain decomposition. In this work we modeled the energy dependency of linear attenuation coefficients in our problem formulation and applied the optimality transfer principle to derive a Poisson-likelihood based algorithm for material decomposition from multiple energy channels. Our algorithm reconstructs the coefficients of the basis functions directly therefore the separate non-linear estimation step in the projection domain as in conventional approaches is avoided. We performed simulations to study the accuracy and noise properties of our method. We synthesized the linear attenuation coefficients at a reference energy and compared with standard attenuation values provided by NIST. We also synthesized the attenuation maps at different effective energy bin centers corresponding to the different energy channels and compared the synthesized images with reconstructions from standard fan-beam FBP methods. Preliminary simulations showed that our reconstructed images have much better noise properties. more...

Novel CdTe photon counting x-ray detectors (PCXDs) have been developed for very high count rates [1-4] suitable for x-ray micro computed tomography (μCT) scanners. It counts photons within each of J energy bins. In this study, we investigate use of the data in these energy bins for material decomposition using an image domain approach. In this method, one image is reconstructed from projection data of each energy bin; thus, we have J images from J energy bins that are associated with attenuation coefficients with a narrow energy width. We assume that the spread of energies in each bin is small and thus that the attenuation can be modeled using an effective energy for each bin. This approximation allows us to linearize the problem, thus simplify the inversion procedure. We then fit J attenuation coefficients at each location x by the energy-attenuation function [5] and obtain either (1) photoelectric and Compton scattering components or (2) 2 or 3 basis-material components. We used computer simulations to evaluate this approach generating projection data with three types of acquisition schemes: (A) five monochromatic energies; (B) five energy bins with PCXD and an 80 kVp polychromatic x-ray spectrum; and (C) two kVp with an intensity integrating detector. Total attenuation coefficients of reconstructed images and calculated effective atomic numbers were compared with data published by National Institute of Standards and Technology (NIST). We developed a new materially defined "SmileyZ" phantom to evaluate the accuracy of the material decomposition methods. Preliminary results showed that material based 3-basis functions (bone, water and iodine) with PCXD with 5 energy bins was the most promising approach for material decomposition. more...

Recently developed solid-state detectors combined with high-speed ASICs that allow individual pixel pulse processing may prove useful as detectors for small animal micro-computed tomography. One appealing feature of these photon-counting x-ray detectors (PCXDs) is their ability to discriminate between photons with different energies and count them in a small number (2-5) of energy windows. The data in these energy windows may be thought of as arising from multiple simultaneous x-ray beams with individual energy spectra, and could thus potentially be used to perform material composition analysis. The goal of this paper was to investigate the potential advantages of PCXDs with multiple energy window counting capability as compared to traditional integrating detectors combined with acquisition of images using x-ray beams with 2 different kVps. For the PCXDs, we investigated 3 potential sources of crosstalk: scatter in the object and detector, limited energy resolution, and pulse piluep. Using Monte Carlo simulations, we showed that scatter in the object and detector results in relatively little crosstalk between the data in the energy windows. To study the effects of energy resolution and pulse-pileup, we performed simulations evaluating the accuracy and precision of basis decomposition using a detector with 2 or 5 energy windows and a single kVp compared to an dual kVp acquisitions with an integrating detector. We found that, for noisy data, the precision of estimating the thickness of two basis materials for a range of material compositions was better for the single kVp multiple energy window acquisitions compared to the dual kVp acquisitions with an integrating detector. The advantage of the multi-window acquisition was somewhat reduced when the energy resolution was reduced to 10 keV and when pulse pileup was included, but standard deviations of the estimated thicknesses remained better by more than a factor of 2. more...

This article discusses how to choose the energy window widths in the problem of basis material decomposition that uses a photon-counting detector which counts photons in several energy windows. Basis material decomposition provides information on object composition by extracting the energy- related information from the number of photons in different detector energy windows. We investigated several candidate energy window parameters in this work and aimed to optimize the performance of basis material decomposition. more...

Tumor necrosis factor alpha (TNFα) is a complicated cytokine which could induce differentiation of acute myeloid leukemia (AML) cells. We have found that Oroxylin A, a natural compound isolated from Scutellariae radix, markedly enhanced TNFα-induced NBT reduction and CD11b/CD14 expression of AML cells. Besides, Giemsa staining also displayed that the combination group induced U937-MDR cells to differentiate into monocyte-like cells yet NB4 and HL-60-resistant cells to granulocytic-like cells. Further study showed that TNFα induced PI3K subunit p85α binding to N-terminal truncated nuclear receptor RXRα (tRXRα) proteins and activating AKT. On the contrary, these could be inhibited by Oroxylin A through inhibiting interaction between tRXRα and p85α in NB4 and HL-60-resistant cells. Moreover, Oroxylin A inhibited the activation of NF-κB signaling and the DNA binding activity by TNFα proved by EMSA in these two AML cells. All these suggested that Oroxylin A was able to inhibit NF-κB signaling and RXRα-dependent AKT signaling, the negative effects of TNFα for AML therapy, suggesting that combination of Oroxylin A and TNFα might be a novel candidate for differentiation therapy for AML cells and required further investigation. Disclosures No relevant conflicts of interest to declare. more...

We previously developed an OS-EM reconstruction method for rotating multi-segment slant-hole SPECT with compensation for non-uniform attenuation and collimator-detector response. In this study we performed simulations to investigate the imaging characteristics of RMSSH SPECT mammography using signal-to-noise ratio as a criterion. We varied the breast lesion size and the lesion to background uptake ratio in the 3D NCAT phantom, reconstructed RMSSH SPECT projection data using OS-EM reconstruction with and without various compensations, and calculated the SNR of the breast lesion from the reconstructed images. For comparison, we also calculated the SNR values using projection images from planar scintimammography. Our calculations showed progressive improvement in terms of SNR values when more compensation for image degrading factors were applied, and RMSSH SPECT offered higher image contrast and SNR values as compared to planar scintimammography. The results from this study may help to design an efficient and economical ROC study for further evaluating the performance in a lesion detection task for RMSSH SPECT mammography. more...

The purpose of this study is to evaluate the performance of four block-iterative algorithms, ordered-subsets expectation-maximization (OS-EM), rescaled block-iterative EM (RBI-EM), modified row-action maximum likelihood algorithm (RAMLA) and rescaled block-iterative maximum a posteriori EM (RBI-MAP-EM), for In-111 ProstaScint/spl reg/ SPECT image reconstruction. The 3D NCAT phantom with realistic In-111 ProstaScint/spl reg/ activity distribution was used in the study. Noise-free and noisy projections of the phantom obtained using a medium-energy general-purpose (MEGP) collimator were generated using Monte Carlo simulation methods. For each algorithm, the projection data were reconstructed with the compensations for attenuation, collimator-detector response and scatter. Image quality was evaluated in terms of FWHM of a profile through a small blood vessel, normalized mean square error (NMSE), ensemble normalized standard deviation (NSDE) of a uniform region of interest (ROI) in the reconstructed image measured from 30 noise realizations, and regional NSD (NSDR) of an ROI measure from 1 noise realization. The results indicated that, RBI-EM has superior performance than that of OS-EM when less than 4 views per subset were used and similar performance when 4 or more views per subset were used. Modified RAMLA provides similar image quality with a slower convergence rate than that of OS-EM. Using well-chosen parameters, RBI-MAP-EM provides increased noise smoothing with less loss in resolution and error. We conclude that when compared with OS-EM, the RBI-EM and modified RAMLA have the same performance at a slower convergence rate, while the RBI-MAP-EM has superior performance and can potentially improve image quality. more...

The purpose of this work is to investigate the effects of different kinds of object variability on the performance of the channelized Hotelling observer (CHO) for detecting defects in myocardial perfusion SPECT using rotating 4-segment slant-hole (R4SSH) and parallel-hole (PH) collimators. In this work, the categories of object variability used were: defect location, uptake ratio and anatomical variations. The effect of each kind of variation alone, the combination of two variations, and mixture of three variations were studied. R4SSH and PH projection data from the 3D NCAT phantom with radioactivity distribution modeling that of Tc-99m Sestamibi were generated using the SIMIND Monte Carlo code. Iterative OS-EM with 4 subsets was used to reconstruct the projections. The number of iteration and the cutoff frequency were optimized for each combination of object variability and imaging method in terms of area under the ROC curve (AUC). The results indicated that R4SSH SPECT allows significantly better myocardial defect detectability than that of PH SPECT when uptake ratio variation alone was included. The differences between defect detectability of R4SSH and PH SPECT became insignificant when defect location and anatomical variations were included in the population. We concluded that, when conducting observer studies to compare different imaging methods, including defect and anatomical variation in the phantom will reduce the statistical power. In clinic, diagnostic accuracy may be improved if radiologists stratify their reading as much as possible. more...

The objective of this research is to optimize and characterize the respiratory gated reconstruction protocol in liver FDG PET scans with non-uniform respiration using Monte-Carlo simulations. Assuming externally-tracked motion information and NCAT respiratory motion model, we compare the standard time gating and optimized amplitude gating methods. Two spherically shaped liver lesions with FWHM of 1 cm and 2 cm are used to evaluate the accuracy of each method in determining the size and the position of the lesions with GE Discovery LS scanner. more...