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Biomedical subjects

Frank P DiFilippo

Publications and source records attributed to Frank P DiFilippo.

9 recordsLinked to original sources

The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI): Overview of consortium sites and anticipated enrollment.

INTRODUCTION: The Consortium for Clarity in Alzheimer's disease related dementias (ADRD) Research Through Imaging (CLARiTI) is a study that aims to collect standardized imaging and plasma biomarkers on 2000 Clinical Core participants enrolled across all Alzheimer's Disease Research Centers (ADRC) sites. We sought to summarize the known heterogeneity across centers regarding scientific focus and initial enrollment plans for CLARiTI. METHODS: We developed and distributed a survey capturing information on the 36 CLARiTI site's theme/expertise, recruitment plans, and the intersection of CLARiTI with other ADRC imaging efforts. RESULTS: Anticipated CLARiTI enrollees spanned 11 different categories of suspected etiologies underlying impairment. A wide range of risk factors were endorsed across sites regarding the enrollment of unimpaired individuals. Variability also existed regarding site-level strategies in enrollment into CLARiTI versus other imaging efforts. DISCUSSION: We anticipate that the 2000 individuals that will enroll into CLARiTI will reflect the clinical heterogeneity already in place across the ADRC network. HIGHLIGHTS: The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will leverage and contribute to the existing Alzheimer's Disease Research Centers (ADRC) program by supporting standardized imaging and plasma collection across all centers. We summarize the variation in scientific focus and enrollment plans across ADRC sites participating in CLARiTI. The anticipated CLARiTI cohort will reflect the clinical heterogeneity that already exists across the ADRC network. CLARiTI will contribute to scientific goals related to the detection of multi-etiological signatures relevant for Alzheimer's disease and related disorders (ADRDs).

Humans↗

Alterations of cellular bioenergetics in pulmonary artery endothelial cells.

Idiopathic pulmonary arterial hypertension (IPAH) is pathogenetically related to low levels of the vasodilator nitric oxide (NO). Because NO regulates cellular respiration and mitochondrial biogenesis, we hypothesized that abnormalities of bioenergetics may be present in IPAH. Evaluation of pulmonary artery endothelial cells from IPAH and control lungs in vitro revealed that oxygen consumption of IPAH cells was decreased, especially in state 3 respiration with substrates glutamate-malate or succinate, and this decrease paralleled reduction in Complex IV activity and IPAH cellular NO synthesis. IPAH pulmonary artery endothelial cells had decreased mitochondrial dehydrogenase activity and lowered mitochondrial numbers per cell and mitochondrial DNA content, all of which increased after exposure to NO donors. Although IPAH/pulmonary artery endothelial cells' ATP content was similar to control under normoxia, cellular ATP did not change significantly in IPAH cells under hypoxia, whereas ATP decreased 35% in control cells, identifying a greater dependence on cellular respiration for energy in control cells. Evidence that glucose metabolism was subserving the primary role for energy requirements of IPAH cells was provided by the approximately 3-fold greater glycolytic rate of IPAH cells. Positron emission tomography scan with [18F]fluoro-deoxy-D-glucose performed on IPAH patients and healthy controls revealed significantly higher uptake in IPAH lungs as compared with controls, confirming that the glycolytic rate was increased in vivo. Thus, there are substantial changes in bioenergetics of IPAH endothelial cells, which may have consequences for pulmonary hypertensive responses and potentially in development of novel imaging modalities for diagnosis and evaluation of treatment.

Adenosine Triphosphate↗

A knowledge-based method for reducing attenuation artefacts caused by cardiac appliances in myocardial PET/CT.

Attenuation artefacts due to implanted cardiac defibrillator leads have previously been shown to adversely impact cardiac PET/CT imaging. In this study, the severity of the problem is characterized, and an image-based method is described which reduces the resulting artefact in PET. Automatic implantable cardioverter defibrillator (AICD) leads cause a moving-metal artefact in the CT sections from which the PET attenuation correction factors (ACFs) are derived. Fluoroscopic cine images were measured to demonstrate that the defibrillator's highly attenuating distal shocking coil moves rhythmically across distances on the order of 1 cm. Rhythmic motion of this magnitude was created in a phantom with a moving defibrillator lead. A CT study of the phantom showed that the artefact contained regions of incorrect, very high CT values and adjacent regions of incorrect, very low CT values. The study also showed that motion made the artefact more severe. A knowledge-based metal artefact reduction method (MAR) is described that reduces the magnitude of the error in the CT images, without use of the corrupted sinograms. The method modifies the corrupted image through a sequence of artefact detection procedures, morphological operations, adjustments of CT values and three-dimensional filtering. The method treats bone the same as metal. The artefact reduction method is shown to run in a few seconds, and is validated by applying it to a series of phantom studies in which reconstructed PET tracer distribution values are wrong by as much as 60% in regions near the CT artefact when MAR is not applied, but the errors are reduced to about 10% of expected values when MAR is applied. MAR changes PET image values by a few per cent in regions not close to the artefact. The changes can be larger in the vicinity of bone. In patient studies, the PET reconstruction without MAR sometimes results in anomalously high values in the infero-septal wall. Clinical performance of MAR is assessed by two physicians' inspection of images generated in 30 patients with and without MAR. Noticeable image differences are judged in 14 of 28 (50%) observations with AICD leads, and significant clinical impact is judged in 2 of 28 (7%) of those observations. A polar map analysis shows significant differences in 10 of 14 (71%) studies with AICD leads, and 0 of 16 (0%) studies without AICD leads. These results show that the MAR method is successful in reducing the magnitude of the metal artefact without incorrectly altering cases without metal artefact. In spite of profound changes to the CT image from the moving metal, the PET ACF in that study was changed by no more than 20%.

Artifacts↗

Do implanted pacemaker leads and ICD leads cause metal-related artifact in cardiac PET/CT?

UNLABELLED: Artifacts related to metallic implants are an established limitation of CT-based attenuation correction (CT-AC) in PET/CT. However, the impact of metallic components of pacemaker leads and implantable cardioverter defibrillator (ICD) leads on the accuracy of cardiac PET has not been evaluated. The goal of this study was to investigate the magnitude of artifacts related to pacing and defibrillation leads in both phantom and patient studies. METHODS: Images were acquired on a PET/CT scanner using CT-AC and were compared with those obtained on a dedicated PET scanner using transmission source-based attenuation correction. Phantoms consisting of pacemaker leads and ICD leads submerged in uniform background activity solution were imaged, and regions were analyzed to measure radionuclide concentrations at known lead locations relative to background. In addition, 15 cardiac 18F-FDG patients (having either pacing leads, defibrillation leads, or both) were imaged on both PET/CT and PET scanners. Images were visually and quantitatively assessed to determine whether artifact related to the implanted leads was present and, if so, its severity relative to surrounding myocardium. RESULTS: In phantom studies, artifacts caused by pacing lead electrodes were barely noticeable, but artifacts arising from highly radioopaque ICD shock coil electrodes were clearly apparent. In the patient studies, no artifacts from pacing leads were identified. However, significant artifact was observed in 50% of the patient studies with ICD leads. In the affected areas, local myocardial uptake in PET/CT images using CT-AC was, on average, 30% higher than that in the corresponding PET images. CONCLUSION: Although pacemaker leads do not appear to cause artifact in cardiac PET/CT images, ICD leads frequently do result in artifacts of sufficient magnitude to impact clinical image interpretation. Accordingly, software-based corrections in CT-AC algorithms appear necessary for accurate cardiac imaging with PET/CT.

Artifacts↗

Porous phantoms for PET and SPECT performance evaluation and quality assurance.

UNLABELLED: Characterization of PET and SPECT imaging performance often requires phantoms with complex radionuclide distributions. For example, lesion detection studies use multiple spherical regions of specific target-to-background ratios to simulate cancerous lesions. Such complex distributions are typically created using phantoms with multiple fillable chambers. However, such phantoms are typically difficult and time-consuming to prepare accurately and reproducibly. A new approach using a single-chamber phantom with a porous core can overcome these difficulties. METHODS: Prototypes of two designs of porous core phantoms were produced and evaluated. The "hot spheres" phantom contained a multitude of simulated spherical lesions with diameters ranging from 6.35 to 25.4 mm ("multi-resolution" slice) and with lesion-to-background ratios ranging from 1.6 to 4.4 ("multi-contrast" slice). The "multi-attenuation" phantom consisted of two halves. One half contained a porous core to produce regions of different attenuation but uniform activity. The other half mimicked the NEMA-94 design with cold inserts of different attenuation. RESULTS: Both phantoms produced the expected radionuclide distributions while requiring the preparation of only a single radionuclide solution and with much reduced preparation time. In images taken on clinical PET and SPECT scanners, the porous core structures were found to contribute negligible background noise or artifact. The measured lesion-to-background ratios from the hot spheres phantom differed slightly from calculated values, with the differences attributed mainly to uncertainty in pore diameter. The measured attenuation coefficients from the multi-attenuation phantom agreed well with expected values. However, it was found that trapped air bubbles due to manufacturing defects in the porous core could potentially cause quantitative errors. CONCLUSION: The hot spheres and multi-attenuation porous phantoms exhibited a wide range of imaging features providing thorough tests of lesion detection and of attenuation and scatter correction accuracy. Because the local activity concentration is set by the relative volume of radionuclide solution in the porous core, the quantitative accuracy is limited mainly by mechanical tolerance, and strict quality control during manufacturing is essential. Nonetheless, the single-chamber design of the porous core phantoms is inherently more reproducible and more practical for routine use compared to conventional multi-chamber phantoms.

Equipment Design↗

Mutual information-based multimodality registration of cardiac ultrasound and SPECT images: a preliminary investigation.

BACKGROUND: Ultrasound (US) and single photon emission computed tomography (SPECT) are the two most commonly prescribed procedures for diagnosing coronary artery disease (CAD). We have demonstrated the feasibility of multimodality registration of two-dimensional (2D) and three-dimensional (3D) cardiac US images with cardiac SPECT images with an aim to simultaneously present the complementary anatomical and perfusion information from the two modalities. We have also tested the clinicians' assessment of the clinical adequacy of the registered images. METHODS AND RESULTS: We have demonstrated temporal and spatial registration for nine sets of cardiac US and SPECT cine loops covering the entire cardiac cycle. Temporal alignment was performed by interpolation of existing SPECT images at cardiac phases corresponding to available US images. Spatial registration was performed in 3D image space using a mutual information-based approach. Experts from echocardiography and nuclear medicine determined the clinical utility of the registration by rating each registration on a scale of 1 to 5, a rating of 3 or above indicating clinical utility. 2DUS-SPECT registration (five cases) received an average rating of 4.2, whereas 3DUS-SPECT registration (four cases) received an average rating of 2.85. By one-sample t test, the overall evaluations (mean 3.58) were greater than the pre-specified clinical cut-off of 3 with p < 0.05, indicating likelihood of clinical utility. CONCLUSION: Our method demonstrates the feasibility of registering cardiac US and SPECT images in their present as well as possible future forms. Such registration has the potential to provide a more accurate and powerful tool for diagnosing CAD.

Clinical Protocols↗

PET performance measurements using the NEMA NU 2-2001 standard.

UNLABELLED: The NU 2-1994 standard document for PET performance measurements has recently been updated. The updated document, NU 2-2001, includes revised measurements for spatial resolution, intrinsic scatter fraction, sensitivity, counting rate performance, and accuracy of count loss and randoms corrections. The revised measurements are designed to allow testing of dedicated PET systems in both 2-dimensional and 3-dimensional modes as well as coincidence gamma cameras, conditions not considered in the original NU 2-1994 standard. In addition, the updated measurements strive toward being more representative of clinical studies, in particular, whole-body imaging. METHODS: Performance measurements following the NU 2-1994 and NU 2-2001 standards were performed on several different PET scanners. Differences between the procedures and resulting performance characteristics, as well as the rationale for these changes, were noted. RESULTS: Spatial resolution is measured with a point source in all 3 directions, rather than a line source, as specified previously. For the measurements of intrinsic scatter fraction, sensitivity, and counting rate performance, a 70-cm line source is now specified, instead of a 19-cm-long cylindric phantom. The longer configuration permits measurement of these performance characteristics over the entire axial field of view of all current PET scanners and incorporates the effects of activity outside the scanner. A measurement of image quality has been added in an effort to measure overall image quality under clinically realistic conditions. This measurement replaces the individual measurements of uniformity and of the accuracy of corrections for attenuation and scatter. CONCLUSION: The changes from the NU 2-1994 standard to the NU 2-2001 standard strive toward establishing relevance with clinical studies. The tests in the updated standard also are, in general, simpler and less time-consuming to perform than those in the NU 2-1994 standard.

Gamma Cameras↗