Name: Video: Novel Alignment-Based Method for Enhancing MicroPET/CT Imaging and Quantitation of Early-Stage Microcalcifications
Uploaded: 2024-11-15T12:40:00
Description: 42 Views. Novel Alignment-Based Method for Enhancing MicroPET/CT Imaging and Quantitation of Early-Stage Microcalcifications

novel alignment-based method for enhancing micropet/ct imaging and quantitation of early-stage microcalcifications

Longitudinal Quantification of Cardiovascular Calcification Using PET/CT Imaging

Cardiovascular disease is a leading global cause of morbidity and mortality, demanding rigorous exploration to uncover its mechanisms and to devise effective preventive and therapeutic strategies. Coronary artery calcification (CAC) is widely acknowledged by the experts in the field as a predictive factor for cardiovascular disease, significantly elevating the risk of cardiovascular mortality1,2,3,4,5. Microscopic calcifications are considered the earliest stages of calcific atherosclerosis, and the term &#34;microcalcifications&#34; has been used to refer to calcium deposits between 0.5 to 50 &#181;m6,7,8,9&#160;in diameter. These small calcifications are believed to coalesce to form larger calcium deposits, fueling the progression of calcific plaque6,7.
Positron emission tomography (PET) and computed tomography (CT) serve as valuable research tools, frequently employed for the non-invasive assessment of cardiovascular calcification in vivo5,10,11,12,13,14,15,16,17,18,19. These imaging modalities prove particularly advantageous for tracking vascular calcification progression in longitudinal studies involving small research animals11,12,13,19. MicroCT imaging has demonstrated effectiveness in providing anatomical images of relatively large calcium deposits11,12,13,19,20. However, its utility for imaging small calcium deposits in living animals is constrained by its spatial resolution of ~100 &#181;m8,14, making it challenging to investigate calcification during its initial phases.
A notable advancement is the adoption of combined microPET/microCT imaging with the PET tracer, fluoride-18-labeled sodium fluoride (18F-NaF), as the standard method for the detection of calcification based on its binding to the mineral surface area. This approach uses radiolabeled 18F-NaF, shown to identify the calcium mineral surface10,13 as the fluoride ions bind covalently to calcium hydroxyapatite, replacing hydroxyl groups to form fluoroapatite21. Consistent with the slower exchange rate relative to the radioactive decay of the 18F (half-life ~110 min) and to the clearance of the tracer through kidneys22, Irkle and colleagues13 found that 18F-NaF binding to calcified carotid specimens was limited to the surface at the time of detection. Thus, tracer uptake should relate directly with mineral surface area, which is greater when a given amount of mineral occurs in multiple small foci or in porous form than when present in few, large, solid deposits. By accentuating the earliest stages of mineralization with high sensitivity, 18F-NaF PET imaging may provide valuable insights into the early stages of disease, making it particularly useful in studying preventive as well as therapeutic strategies13,14,15.
Even with recent advancements in the combined microPET/microCT imaging of vascular calcification, there are opportunities for improving the accuracy of image analysis in longitudinal, cardiovascular calcification studies. Conventional approaches use labor-intensive, manual delineation of regions of interest (ROI) around each visible calcified region in every mouse at each individual time point throughout the longitudinal study. This method reduces precision, particularly in the early disease stages when the sizes of calcium deposits approach the scanners&#39; detection limits, potentially making invisible some areas with minuscule deposits arranged in low density.
In the realm of imaging, alignment generally refers to the spatial alignment of a series of images. Introducing alignment as a novel solution to the existing challenges, our proposed method allows investigators to use a consistent location for following the progression of calcification in serial images from individual subjects throughout a longitudinal study. Given that tissue calcification is known to arise from nanosized matrix vesicles (50-150 nm), which coalesce to form microscopic, then macroscopic hydroxyapatite mineral23, one may retrospectively identify where microcalcifications would have been located in early images before they are discernable.
Following that same location over time, made possible by image alignment, is the basis for this method. It obviates the need to identify the earliest calcification stages directly, as the ROI&#160;is assigned based on the latest stages when mineralization is readily identified. In this protocol, we present an improved, streamlined data analysis method that incorporates the alignment of a time series of images as a vital step, enhancing accurate quantitation of calcium deposition in longitudinal, combined, microPET/microCT imaging studies (Figure 1). While we use PET/CT data analysis as an example, this method can be applied to the analyses of other longitudinal imaging data, including single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and optical imaging24.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66805/66805fig01.jpg" /> 
Figure 1: Protocol overview flowchart. Flowchart summarizing the novel protocol for quantifying cardiovascular calcification. General steps include longitudinal imaging, alignment of images acquired at different time points, and segmentation and quantification of the calcified region. <a href="https://www.jove.com/files/ftp_upload/66805/66805fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Author Spotlight: Enhanced Quantification of Cardiovascular Calcification Progression for Longitudinal Micro PET/CT Studies in Small Research Animals

Novel Quantification Protocol for Cardiovascular Calcification Progression Using Longitudinal MicroPET/MicroCT Images

Novel Alignment-Based Method for Enhancing MicroPET/CT Imaging and Quantitation of Early-Stage Microcalcifications

novel-alignment-based-method-for-enhancing-micropetct-imaging

Research

JoVE Journal

Medicine

42 Views. Novel Alignment-Based Method for Enhancing MicroPET/CT Imaging and Quantitation of Early-Stage Microcalcifications

Video: Novel Alignment-Based Method for Enhancing MicroPET/CT Imaging and Quantitation of Early-Stage Microcalcifications

Micro positron emission tomography (PET) and micro computed tomography (CT) imaging are powerful, ideal research tools for following the progression of cardiovascular calcification. Due to their non-invasive nature, small research animals can be imaged at multiple time points. The challenge lies in the accurate quantification of cardiovascular calcification. Here, we provide a protocol, using images from the later disease stages as a template, to accurately quantify the progression of cardiovascular calcification in longitudinal studies. The protocol involves 1) the alignment of the chest area in multiple images from the same animal during a longitudinal study as the first step, 2) the definition of a region of interest (ROI) situated within the heart and the aorta at the site of larger calcium deposits that become apparent in later images, and 3) simultaneous segmentation and quantification of calcium deposits across all images acquired during the longitudinal study. This streamlined method enhances the accuracy of image analysis in following the progression of cardiovascular calcification by improving the precision of ROI definition and reducing the variability associated with earlier techniques that analyze individual scans independently.

This novel protocol entails the quantification of cardiovascular calcification progression from serial micro positron emission tomography (PET)/micro computed tomography (CT) images in small research animals.

Micro positron emission tomography (PET) and micro computed tomography (CT) imaging are powerful, ideal research tools for following the progression of ...