Grouped-Coordinate Ascent Algorithms for Penalized-Likelihood Transmission Image Reconstruction

Presents a new class of algorithms for penalized-likelihood reconstruction of attenuation maps from low-count transmission scans. We derive the algorithms by applying to the transmission log-likelihood a version of the convexity technique developed by De Pierro for emission tomography. The new class includes the single-coordinate ascent (SCA) algorithm and Lange's convex algorithm for transmission tomography as special cases. The new grouped-coordinate ascent (GCA) algorithms in the class overcome several limitations associated with previous algorithms. (1) Fewer exponentiations are required than in the transmission maximum likelihood-expectation maximization (ML-EM) algorithm or in the SCA algorithm. (2) The algorithms intrinsically accommodate nonnegativity constraints, unlike many gradient-based methods. (3) The algorithms are easily parallelizable, unlike the SCA algorithm and perhaps line-search algorithms. We show that the GCA algorithms converge faster than the SCA algorithm, even on conventional workstations. An example from a low-count positron emission tomography (PET) transmission scan illustrates the method.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86021/1/Fessler93.pd

In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease

To map presynaptic cholinergic terminal densities in normal aging (n = 36), Alzheimer's disease (AD) (n = 22), and Parkinson's disease (PD) (n = 15), we performed single-photon emission computed tomography using [ 123 I]iodoben-zovesamicol (IBVM), an in vivo marker of the vesicular acetylcholine transporter. We used coregistered positron emission tomography with [ 18 F]fluorodexyglucose for metabolic assessment and coregistered magnetic resonance imaging for atrophy assessment. In controls (age, 22–91 years), cortical IBVM binding declined only 3.7% per decade. In AD, cortical binding correlated inversely with dementia severity. In mild dementia, binding differed according to age of onset, but metabolism did not. With an onset age of less than 65 years, binding was reduced severely throughout the entire cerebral cortex and hippocapus (about 30%), but with an onset age of 65 years or more, binding reductions were restricted to temporal cortex and hippocampus. In PD without dementia, binding was reduced only in parietal and occipital cortex, but demented PD subjects had extensive cortical binding decreases similar to early-onset AD. We conclude that cholinergic neuron integrity can be monitored in living AD and PD patients, and that it is not so devastated in vivo as suggested by postmortem choline acetylransferase activity (50–80%).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50361/1/410400309_ftp.pd

Quantification of Myocardial Blood Flow in Absolute Terms Using (82)Rb PET Imaging: The RUBY-10 Study.

OBJECTIVES: The purpose of this study was to compare myocardial blood flow (MBF) and myocardial flow reserve (MFR) estimates from rubidium-82 positron emission tomography ((82)Rb PET) data using 10 software packages (SPs) based on 8 tracer kinetic models. BACKGROUND: It is unknown how MBF and MFR values from existing SPs agree for (82)Rb PET. METHODS: Rest and stress (82)Rb PET scans of 48 patients with suspected or known coronary artery disease were analyzed in 10 centers. Each center used 1 of 10 SPs to analyze global and regional MBF using the different kinetic models implemented. Values were considered to agree if they simultaneously had an intraclass correlation coefficient >0.75 and a difference <20% of the median across all programs. RESULTS: The most common model evaluated was the Ottawa Heart Institute 1-tissue compartment model (OHI-1-TCM). MBF values from 7 of 8 SPs implementing this model agreed best. Values from 2 other models (alternative 1-TCM and Axially distributed) also agreed well, with occasional differences. The MBF results from other models (e.g., 2-TCM and retention) were less in agreement with values from OHI-1-TCM. CONCLUSIONS: SPs using the most common kinetic model-OHI-1-TCM-provided consistent results in measuring global and regional MBF values, suggesting that they may be used interchangeably to process data acquired with a common imaging protocol

Validation of a new automated method for analysis of gated-SPECT images

We recently presented a new method for quantification of CArdiac FUnction - denoted CAFU - as the first step in the development of an automated method for integrated interpretation of gated myocardial perfusion single photon emission computed tomography (SPECT) images. The aim of this study was to validate CAFU in the assessment of global and regional function of the left ventricle. Quantitative gated-SPECT (QGS), the most widely used software package for quantification of gated-SPECT images, was used as reference method for the measurements of ejection fraction (EF) and ventricular volumes, and visual analysis by an experienced physician was used as reference method for the measurements of regional wall motion and thickening. Two different groups of consecutive patients referred for myocardial perfusion scintigraphy were studied. Global function was evaluated in 316 patients and regional function in 49 other patients. The studies were performed using a 2-day stress/rest 99 m-Tc-sestamibi protocol. A good correlation was found between EF values from QGS and CAFU (EF CAFU = 0.84 EF QGS + 13, r = 0.94), but CAFU values were on average 4 EF points higher than QGS values. With CAFU the segments with normal thickening according to the physician showed significantly higher thickening values (in all parts of the myocardium) compared to the segments classified as having abnormal thickening. In conclusion, this study demonstrates that CAFU can be used to quantify global and regional function in gated-SPECT images. This is an important step in our development of an automated method for integrated interpretation of gated-SPECT myocardial perfusion scintigraphy studies

A new automated method for analysis of gated-SPECT images based on a three-dimensional heart shaped model

A new automated method for quantification of left ventricular function from gated-single photon emission computed tomography ( SPECT) images has been developed. The method for quantification of cardiac function (CAFU) is based on a heart shaped model and the active shape algorithm. The model contains statistical information of the variability of left ventricular shape. CAFU was adjusted based on the results from the analysis of five simulated gated-SPECT studies with well defined volumes of the left ventricle. The digital phantom NURBS-based Cardiac-Torso (NCAT) and the Monte-Carlo method SIMIND were used to simulate the studies. Finally CAFU was validated on ten rest studies from patients referred for routine stress/rest myocardial perfusion scintigraphy and compared with Cedar-Sinai quantitative gated-SPECT (QGS), a commercially available program for quantification of gated-SPECT images. The maximal differences between the CAFU estimations and the true left ventricular volumes of the digital phantoms were 11 ml for the end-diastolic volume (EDV), 3 ml for the end-systolic volume (ESV) and 3% for the ejection fraction (EF). The largest differences were seen in the smallest heart. In the patient group the EDV calculated using QGS and CAFU showed good agreement for large hearts and higher CAFU values compared with QGS for the smaller hearts. In the larger hearts, ESV was much larger for QGS than for CAFU both in the phantom and patient studies. In the smallest hearts there was good agreement between QGS and CAFU. The findings of this study indicate that our new automated method for quantification of gated-SPECT images can accurately measure left ventricular volumes and EF

Proteomic Landscape of Tissue-Specific Cyclin E Functions in Vivo

E-type cyclins (cyclins E1 and E2) are components of the cell cycle machinery that has been conserved from yeast to humans. The major function of E-type cyclins is to drive cell division. It is unknown whether in addition to their ‘core’ cell cycle functions, E-type cyclins also perform unique tissue-specific roles. Here, we applied high-throughput mass spectrometric analyses of mouse organs to define the repertoire of cyclin E protein partners in vivo. We found that cyclin E interacts with distinct sets of proteins in different compartments. These cyclin E interactors are highly enriched for phosphorylation targets of cyclin E and its catalytic partner, the cyclin-dependent kinase 2 (Cdk2). Among cyclin E interactors we identified several novel tissue-specific substrates of cyclin E-Cdk2 kinase. In proliferating compartments, cyclin E-Cdk2 phosphorylates Lin proteins within the DREAM complex. In the testes, cyclin E-Cdk2 phosphorylates Mybl1 and Dmrtc2, two meiotic transcription factors that represent key regulators of spermatogenesis. In embryonic and adult brains cyclin E interacts with proteins involved in neurogenesis, while in adult brains also with proteins regulating microtubule-based processes and microtubule cytoskeleton. We also used quantitative proteomics to demonstrate re-wiring of the cyclin E interactome upon ablation of Cdk2. This approach can be used to study how protein interactome changes during development or in any pathological state such as aging or cancer