Multi-Level Canonical Correlation Analysis for Standard-Dose PET Image Estimation

Positron emission tomography (PET) images are widely used in many clinical applications such as tumor detection and brain disorder diagnosis. To obtain PET images of diagnostic quality, a sufficient amount of radioactive tracer has to be injected into a living body, which will inevitably increase the risk of radiation exposure. On the other hand, if the tracer dose is considerably reduced, the quality of the resulting images would be significantly degraded. It is of great interest to estimate a standard-dose PET (S-PET) image from a low-dose one in order to reduce the risk of radiation exposure and preserve image quality. This may be achieved through mapping both standard-dose and low-dose PET data into a common space and then performing patch based sparse representation. However, a one-size-fits-all common space built from all training patches is unlikely to be optimal for each target S-PET patch, which limits the estimation accuracy. In this paper, we propose a data-driven multi-level Canonical Correlation Analysis (mCCA) scheme to solve this problem. Specifically, a subset of training data that is most useful in estimating a target S-PET patch is identified in each level, and then used in the next level to update common space and improve estimation. Additionally, we also use multi-modal magnetic resonance images to help improve the estimation with complementary information. Validations on phantom and real human brain datasets show that our method effectively estimates S-PET images and well preserves critical clinical quantification measures, such as standard uptake value

Prediction of standard-dose brain PET image by using MRI and low-dose brain [ 18 F]FDG PET images: Prediction of standard-dose brain PET image

Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient’s exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [18F]FDG PET image by using a low-dose brain [18F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image

Design and characterization of a spatially distributed multibeam field emission x-ray source for stationary digital breast tomosynthesis: Stationary digital breast tomosynthesis

Digital breast tomosynthesis (DBT) is a limited angle computed tomography technique that can distinguish tumors from its overlying breast tissues and has potentials for detection of cancers at a smaller size and earlier stage. Current prototype DBT scanners are based on the regular full-field digital mammography systems and require partial isocentric motion of an x-ray tube over certain angular range to record the projection views. This prolongs the scanning time and, in turn, degrades the imaging quality due to motion blur. To mitigate the above limitations, the concept of a stationary DBT (s-DBT) scanner has been recently proposed based on the newly developed spatially distributed multibeam field emission x-ray (MBFEX) source technique using the carbon nanotube. The purpose of this article is to evaluate the performance of the 25-beam MBFEX source array that has been designed and fabricated for the s-DBT system. The s-DBT system records all the projection images by electronically activating the multiple x-ray beams from different viewing angles without any mechanical motion. The configuration of the MBFEX source is close to the published values from the Siemens Mammomat system. The key issues including the x-ray flux, focal spot size, spatial resolution, scanning time, beam-to-beam consistency, and reliability are evaluated using the standard procedures. In this article, the authors describe the design and performance of a distributed x-ray source array specifically designed for the s-DBT system. They evaluate the emission current, current variation, lifetime, and focal spot sizes of the source array. An emission current of up to 18 mA was obtained at 0.5×0.3 mm effective focal spot size. The experimentally measured focal spot sizes are comparable to that of a typical commercial mammography tube without motion blurring. Trade-off between the system spatial resolution, x-ray flux, and scanning time are also discussed. Projection images of a breast phantom were collected using the x-ray source array from 25 different viewing angles without motion. These preliminary results demonstrate the feasibility of the proposed s-DBT scanner. The technology has the potential to increase the resolution and reduce the imaging time for DBT. With the present design of 25 views, they demonstrated experimentally the feasibility of achieving 11 s scanning time at full detector resolution with 0.5×0.3 mm source resolution without motion blur. The flexibility in configuration of the x-ray source array will also allow system designers to consider imaging geometries that are difficult to achieve with the conventional single-source rotating approach

Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library

We developed a screening procedure to identify ligands from a phage display random peptide library that are selective for circulating bone marrow derived cells homing to angiogenic tumors. Panning the library on blood outgrowth endothelial cell suspension in vitro followed by in vivo selection based on homing of bone marrow-bound phage to angiogenic tumors, yielded the peptide QFPPKLTNNSML. Upon intravenous injection phage displaying this peptide homed to Lewis lung carcinoma (LLC) tumors in vivo whereas control phage did not localize to tumor tissue. Phage carrying the QFPPKLTNNSML peptide labeled with 64Cu radionuclide when administered intravenously into a tumor bearing mouse was detected noninvasively with positron emission tomography (PET) around the tumor. These proof-of-principle experiments demonstrate the ability of the QFPPKLTNNSML peptide to deliver payload (radiolabeled phage conjugates) in vivo to sites of ongoing angiogenesis and point to its potential clinical utility in a variety of physiologic and pathologic processes where neovascular growth is a critical component

Cyclic Tensile Strain Enhances Osteogenesis and Angiogenesis in Mesenchymal Stem Cells from Osteoporotic Donors

We have shown that the uniaxial cyclic tensile strain of magnitude 10% promotes and enhances osteogenesis of human mesenchymal stem cells (hMSC) and human adipose-derived stem cells (hASC) from normal, nonosteoporotic donors. In the present study, MSC from osteoporotic donors were analyzed for changes in mRNA expression in response to 10% uniaxial tensile strain to identify potential mechanisms underlying the use of this mechanical loading paradigm for prevention and treatment of osteoporosis. Human MSC isolated from three female, postmenopausal osteoporotic donors were analyzed for their responses to mechanical loading using microarray analysis of over 47,000 gene probes. Human MSC were seeded in three-dimensional collagen type I constructs to mimic the organic extracellular matrix of bone and 10% uniaxial cyclic tensile strain was applied to promote osteogenesis. Seventy-nine genes were shown to be regulated within hMSC from osteoporotic donors in response to 10% cyclic tensile strain. Upregulation of six genes were further confirmed with real-time RT-PCR: jun D proto-oncogene (JUND) and plasminogen activator, urokinase receptor (PLAUR), two genes identified as potential key molecules from network analysis; phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD) and wingless-type MMTV integration site family, member 5B (WNT5B), two genes with known importance in bone biology; and, PDZ and LIM domain 4 (PDLIM4) and vascular endothelial growth factor A (VEGFA), two genes that we have previously shown are significantly regulated in hASC in response to this mechanical stimulus. Function analysis indicated that 10% cyclic tensile strain induced expression of genes associated with cell movement, cell proliferation, and tissue development, including development in musculoskeletal and cardiovascular systems. Our results demonstrate that hMSC from aged, osteoporotic donors are capable of enhanced osteogenic differentiation in response to 10% cyclic tensile strain with significant increases in the expression of genes associated with enhanced cell proliferation, musculoskeletal development, and angiogenesis. Surprisingly, cyclic tensile strain of magnitude 10% not only enhanced osteogenesis in hMSC from osteoporotic donors, but also enhanced expression of angiogenic factors. Better understanding and methodologies to promote osteogenesis in hMSC from elderly, osteoporotic donors may greatly facilitate achieving long-term success in bone regeneration and functional bone tissue engineering for this ever-growing patient population

MR-based attenuation correction for PET/MRI neurological studies with continuous-valued attenuation coefficients for bone through a conversion from R2* to CT-Hounsfield units

AIM: MR-based correction for photon attenuation in PET/MRI remains challenging, particularly for neurological applications requiring quantitation of data. Existing methods are either not sufficiently accurate or are limited by the computation time required. The goal of this study was to develop an MR-based attenuation correction method that accurately separates bone tissue from air and provides continuous-valued attenuation coefficients for bone. MATERIALS AND METHODS: PET/MRI and CT datasets were obtained from 98 subjects (mean age [±SD]: 66yrs [±9.8], 57 females) using an IRB-approved protocol and with informed consent. Subjects were injected with 352±29MBq of (18)F-Florbetapir tracer, and PET acquisitions were begun either immediately or 50min after injection. CT images of the head were acquired separately using a PET/CT system. Dual echo ultrashort echo-time (UTE) images and two-point Dixon images were acquired. Regions of air were segmented via a threshold of the voxel-wise multiplicative inverse of the UTE echo 1 image. Regions of bone were segmented via a threshold of the R2* image computed from the UTE echo 1 and UTE echo 2 images. Regions of fat and soft tissue were segmented using fat and water images decomposed from the Dixon images. Air, fat, and soft tissue were assigned linear attenuation coefficients (LACs) of 0, 0.092, and 0.1cm(-1), respectively. LACs for bone were derived from a regression analysis between corresponding R2* and CT values. PET images were reconstructed using the gold standard CT method and the proposed CAR-RiDR method. RESULTS: The RiDR segmentation method produces mean Dice coefficient±SD across subjects of 0.75±0.05 for bone and 0.60±0.08 for air. The CAR model for bone LACs greatly improves accuracy in estimating CT values (28.2%±3.0 mean error) compared to the use of a constant CT value (46.9%±5.8, p<10(-6)). Finally, the CAR-RiDR method provides a low whole-brain mean absolute percent-error (MAPE±SD) in PET reconstructions across subjects of 2.55%±0.86. Regional PET errors were also low and ranged from 0.88% to 3.79% in 24 brain ROIs. CONCLUSION: We propose an MR-based attenuation correction method (CAR-RiDR) for quantitative PET neurological imaging. The proposed method employs UTE and Dixon images and consists of two novel components: 1) accurate segmentation of air and bone using the inverse of the UTE1 image and the R2* image, respectively and 2) estimation of continuous LAC values for bone using a regression between R2* and CT-Hounsfield units. From our analysis, we conclude that the proposed method closely approaches (<3% error) the gold standard CT-scaled method in PET reconstruction accuracy

Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression

ccRCC has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We’ve recently employed the novel positron emission tomography/magnetic resonance (PET/MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans

Improved Dynamic Cardiac Phantom Based on 4D NURBS and Tagged MRI

We previously developed a realistic phantom for the cardiac motion for use in medical imaging research. The phantom was based upon a gated magnetic resonance imaging (MRI) cardiac study and using 4D non-uniform rational b-splines (NURBS). Using the gated MRI study as the basis for the cardiac model had its limitations. From the MRI images, the change in the size and geometry of the heart structures could be obtained, but without markers to track the movement of points on or within the myocardium, no explicit time correspondence could be established for the structures. Also, only the inner and outer surfaces of the myocardium could be modeled. We enhance this phantom of the beating heart using 4D tagged MRI data. We utilize NURBS surfaces to analyze the full 3D motion of the heart from the tagged data. From this analysis, time-dependent 3D NURBS surfaces were created for the right (RV) and left ventricles (LV). Models for the atria were developed separately since the tagged data only covered the ventricles. A 4D NURBS surface was fit to the 3D surfaces of the heart creating time-continuous 4D NURBS models. Multiple 4D surfaces were created for the left ventricle (LV) spanning its entire volume. The multiple surfaces for the LV were spline-interpolated about an additional dimension, thickness, creating a 4D NURBS solid model for the LV with the ability to represent the motion of any point within the volume of the LV myocardium at any time during the cardiac cycle. Our analysis of the tagged data was found to produce accurate models for the RV and LV at each time frame. In a comparison with segmented structures from the tagged dataset, LV and RV surface predictions were found to vary by a maximum of 1.5 mm\u27s and 3.4 mm\u27s respectively. The errors can be attributed to the tag spacing in the data (7.97 mm\u27s). The new cardiac model was incorporated into the 4D NURBS-based Cardiac-Torso (NCAT) phantom widely used in imaging research. With its enhanced abilities, the model will provide a useful tool in the study of cardiac imaging and the effects of cardiac motion in medical images