Feasibility of Template-Guided Attenuation Correction in Cat Brain PET Imaging

Purpose  

Attenuation correction (AC) is important in quantitative positron emission tomography (PET) imaging of medium-sized animals such as the cat. However, additional time for transmission (TX) scanning and tracer uptake is required in PET studies with animal-dedicated PET scanners because post-injection TX scanning is not available in these systems. The aim of this study was to validate a template-guided AC (TGAC) method that does not require TX PET data for AC in cat 2-deoxy-2-[F-¹⁸fluoro-D-glucose (FDG) brain PET imaging.     

Comparative Assessment of Energy-Mapping Approaches in CT-Based Attenuation Correction for PET

Introduction  

Reliable quantification in positron emission tomography (PET) requires accurate attenuation correction of emission data, which in turn entails accurate determination of the attenuation map (μ-map) of the object under study. One of the main steps involved in CT-based attenuation correction (CTAC) is energy-mapping, or the conversion of linear attenuation coefficients (μ) calculated at the effective CT energy to those corresponding to 511 keV.     

Single STE-MR Acquisition in MR-Based Attenuation Correction of Brain PET Imaging Employing a Fully Automated and Reproducible Level-Set Segmentation Approach

Purpose

The aim of this study is to introduce a fully automatic and reproducible short echo-time (STE) magnetic resonance imaging (MRI) segmentation approach for MR-based attenuation correction of positron emission tomography (PET) data in head region.

Procedures

Single STE-MR imaging was followed by generating attenuation correction maps (μ-maps) through exploiting an automated clustering-based level-set segmentation approach to classify head images into three regions of cortical bone, air, and soft tissue. Quantitative assessment was performed by comparing the STE-derived region classes with the corresponding regions extracted from X-ray computed tomography (CT) images.

Results

The proposed segmentation method returned accuracy and specificity values of over 90 % for cortical bone, air, and soft tissue regions. The MR- and CT-derived μ-maps were compared by quantitative histogram analysis.

Conclusions

The results suggest that the proposed automated segmentation approach can reliably discriminate bony structures from the proximal air and soft tissue in single STE-MR images, which is suitable for generating MR-based μ-maps for attenuation correction of PET data.

     

Quantitative Effects of Contrast Enhanced CT Attenuation Correction on PET SUV Measurements

Purpose The presence of contrast materials on computed tomography (CT) images can cause problems in the attenuation correction of positron emission tomography (PET) images. These are because of errors converting the CT attenuation of contrast to 511-keV attenuation and by the change in tissue enhancement over the duration of the PET emission scan. Newer CT-based attenuation correction (CTAC) algorithms have been developed to reduce these errors. Methods To evaluate the effectiveness of the modified CTAC technique, we performed a retrospective analysis on 20 patients, comparing PET images using unenhanced and contrast-enhanced CT scans for attenuation correction. A phantom study was performed to simulate the effects of contrast on radiotracer concentration measurements. Results There was a maximum difference in calculated radiotracer concentrations of 5.9% within the retrospective data and 7% within the phantom data. Conclusion Using a CTAC algorithm that de-emphasizes high-density areas, contrast-enhanced CT can be used for attenuation mapping without significant errors in quantitation.     

Scatter Characterization and Correction for Simultaneous Multiple Small-Animal PET Imaging

Purpose

The rapid growth and usage of small-animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However, this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is, first, to characterize the magnitude and spatial distribution of the scatter component in small-animal PET imaging when scanning single and multiple rodents simultaneously and, second, to assess the relevance and evaluate the performance of scatter correction under similar conditions.

Methods

The LabPET?-8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape-based and more realistic voxel-based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single-scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small-animal PET imaging evaluated in terms of image quality and quantitative accuracy.

Results

A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single- and multiple-subject imaging. In the LabPET?-8 scanner, the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out-of field-of-view (FOV) scatter fraction (SF) is 1.70, 0.76, and 0.11 % for lower energy thresholds of 250, 350, and 400 keV, respectively. The increase in SF ranged between 25 and 64 % when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill-over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole-body and rat whole-body anatomical models were improved for multiple imaging studies following scatter correction.

Conclusions

The magnitude and spatial distribution of the scatter component in small-animal PET imaging of single and multiple subjects simultaneously were characterized, and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies, whereas its impact is insignificant in single mouse imaging.     

Ultrasound Attenuation Estimation in Harmonic Imaging for Robust Fatty Liver Detection

Accurate detection of liver steatosis is important for liver disease management. Ultrasound attenuation coefficient estimation (ACE) has great potential in quantifying liver fat content. The commonly used ACE methods (e.g., spectral shift methods, reference phantom methods) assume linear tissue response to ultrasound and were developed in fundamental imaging. However, fundamental imaging may be vulnerable to reverberation clutters introduced by the body wall. The clutters superimposed on liver echoes may bias the attenuation estimation. Here we propose a new ACE technique, the reference frequency method (RFM), in harmonic imaging to mitigate the reverberation bias. The accuracy of harmonic RFM was validated through a phantom study. In a pilot patient study, harmonic RFM performed more robustly in vivo compared with fundamental RFM, illustrating the potential of ACE in harmonic imaging.     

Multidirectional Estimation of Arterial Stiffness Using Vascular Guided Wave Imaging with Geometry Correction

We previously found that vascular guided wave imaging (VGWI) could non-invasively quantify transmural wall stiffness in both the longitudinal (r–z plane, 0°) and circumferential (r–θ plane, 90°) directions of soft hollow cylinders. Arterial stiffness estimation in multiple directions warrants further comprehensive characterization of arterial health, especially in the presence of asymmetric plaques, but is currently lacking. This study therefore investigated the multidirectional estimation of the arterial Young's modulus in a finite-element model, in vitro artery-mimicking phantoms and an excised porcine aorta. A longitudinal pre-stretch of 20% and/or lumen pressure (15 or 70?mm Hg) was additionally introduced to pre-condition the phantoms for emulating the intrinsic mechanical anisotropy of the real artery. The guided wave propagation was approximated by a zero-order antisymmetric Lamb wave model. Shape factor, which was defined as the ratio of inner radius to thickness, was calculated over the entire segment of each planar cross section of the hollow cylindrical structure at a full rotation (0°–360° at 10° increments) about the radial axis. The view-dependent geometry of the cross segment was found to affect the guided wave propagation, causing Young's modulus overestimation in four angular intervals along the propagation pathway, all of which corresponded to wall regions with low shape factors (<1.5). As validated by mechanical tensile testing, the results indicate not only that excluding the propagation pathway with low shape factors could correct the overestimation of Young's modulus, but also that VGWI could portray the anisotropy of hollow cylindrical structures and the porcine aorta based on the derived fractional anisotropy values from multidirectional modulus estimates. This study may serve as an important step toward 3-D assessment of the mechanical properties of the artery.     

人体组织超声衰减成像新技术

目的 :建立和发展一种新的人体超声组织衰减成像方法。方法 :将超声脉冲回波信号中的组织衰减分量通过一联机的计算机及专门算法提取处理并逐点成像。通过对感兴趣区的直方图测量可对组织衰减值进行定量估算。结果 :已取得了一些脏器组织正常和病理状态的超声衰减图像 ,提供了有价值和前所未有的组织结构和病理状况信息。结论 :人体组织衰减成像原理正确、方法可行。本项研究工作有待进一步深化     

Attenuation Coefficient Estimation of Normal Placentas

Attenuation coefficient estimation has the potential to be a useful tool for placental tissue characterization. A current challenge is the presence of inhomogeneities in biological tissue that result in a large variance in the attenuation coefficient estimate (ACE), restricting its clinical utility. In this work, we propose a new Attenuation Estimation Region Of Interest (AEROI) selection method for computing the ACE based on the (i) envelope signal-to-noise ratio deviation and (ii) coefficient of variation of the transmit pulse bandwidth. The method was first validated on a tissue-mimicking phantom, for which an 18%–21% reduction in the standard deviation of ACE and a 14%–24% reduction in the ACE error, expressed as a percentage of reported ACE, were obtained. A study on 59 post-delivery clinically normal placentas was then performed. The proposed AEROI selection method reduced the intra-subject standard deviation of ACE from 0.72 to 0.39 dB/cm/MHz. The measured ACE of 59 placentas was 0.77 ± 0.37 dB/cm/MHz, which establishes a baseline for future studies on placental tissue characterization.     

Improved Ultrasound Attenuation Estimation with Non-uniform Structure Detection and Removal

Accurate detection of liver steatosis is important for liver disease management. Ultrasound attenuation coefficient estimation (ACE) has great potential in quantifying liver fat content. The ACE methods commonly assume uniform tissue characteristics. However, in vivo tissues typically contain non-uniform structures, which may bias the attenuation estimation and lead to large standard deviations. Here we propose a series of non-uniform structure detection and removal (NSDR) methods to reduce the impact from non-uniform structures during ACE analysis. The effectiveness of NSDR was validated through phantom and in vivo studies. In a pilot clinical study, ACE with NSDR provided more robust in vivo performance as compared with ACE without NSDR, indicating its potential for in vivo applications.     

Impact of a Multiple Mice Holder on Quantitation of High-Throughput MicroPET Imaging With and Without Ct Attenuation Correction

Purpose

The aim of this study is to evaluate the impact of scanning multiple mice simultaneously on image quantitation, relative to single mouse scans on both a micro-positron emission tomography/computed tomography (microPET/CT) scanner (which utilizes CT-based attenuation correction to the PET reconstruction) and a dedicated microPET scanner using an inexpensive mouse holder “hotel.”

Methods

We developed a simple mouse holder made from common laboratory items that allows scanning multiple mice simultaneously. It is also compatible with different imaging modalities to allow multiple mice and multi-modality imaging. For this study, we used a radiotracer (⁶⁴Cu-GB170) with a relatively long half-life (12.7 h), selected to allow scanning at times after tracer uptake reaches steady state. This also reduces the effect of decay between sequential imaging studies, although the standard decay corrections were performed. The imaging was also performed using a common tracer, 2-deoxy-2-[¹⁸ F]fluoro-d-glucose (FDG), although the faster decay and faster pharmacokinetics of FDG may introduce greater biological variations due to differences in injection-to-scan timing. We first scanned cylindrical mouse phantoms (50 ml tubes) both in a groups of four at a time (multiple mice mode) and then individually (single mouse mode), using microPET/CT and microPET scanners to validate the process. Then, we imaged a first set of four mice with subcutaneous tumors (C2C12Ras) in both single- and multiple-mice imaging modes. Later, a second set of four normal mice were injected with FDG and scanned 1 h post-injection. Immediately after completion of the scans, ex vivo biodistribution studies were performed on all animals to provide a “gold-standard” to compare quantitative values obtained from PET. A semi-automatic threshold-based region of interest tool was used to minimize operator variability during image analysis.

Results

Phantom studies showed less than 4.5 % relative error difference between the single- and multiple-mice imaging modes of PET imaging with CT-based attenuation correction and 18.4 % without CT-based attenuation correction. In vivo animal studies (n?=?4) showed <5 % (for ⁶⁴Cu, p?>?0.686) and <15 % (for FDG, p?>?0.4 except for brain image data p?=?0.029) relative mean difference with respect to percent injected dose per gram (%ID/gram) between the single- and multiple-mice microPET imaging mode when CT-based attenuation correction is performed. Without CT-based attenuation correction, we observed relative mean differences of about 11 % for ⁶⁴Cu and 15 % for FDG.

Conclusion

Our results confirmed the potential use of a microPET/CT scanner for multiple mice simultaneous imaging without significant sacrifice in quantitative accuracy as well as in image quality. Thus, the use of the mouse “hotel” is an aid to increasing instrument throughput on small animal scanners with minimal loss of quantitative accuracy.     

Reproducibility of Semi-quantitative Parameters in FDG-PET Using Two Different PET Scanners: Influence of Attenuation Correction Method and Examination Interval

Purpose The aim of this study is to evaluate the reproducibility of semi-quantitative parameters obtained from two 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography (FDG–PET) studies using two different PET scanners. Methods Forty-five patients underwent FDG–PET examination with two different PET scanners on separate days. Two PET images with different attenuation correction method were generated in each patient, and three regions of interest (ROIs) were placed on the lung tumor and normal organs (mediastinum and liver) in each image. Mean and maximum standardized uptake values (SUVs), tumor-to-mediastinum and tumor-to-liver ratios (T/M and T/L), and the percentage difference in parameters between two PET images (% Diff.) were compared. Results All measured values except maximum SUV in the liver and tumor-related parameters (SUV in lung tumor, T/M, T/L) showed no significant difference between two PET images. Conclusion The mean measured values showed high reproducibility and demonstrate that follow-up study or measurement of tumor response to anticancer drugs can be undertaken by FDG–PET examination without specifying the particular type of PET scanner.     

Flow Quantification with Nakagami Parametric Imaging for Suppressing Contrast Microbubbles Attenuation

Flow quantification with contrast-enhanced ultrasound is still limited by the effects of contrast microbubble attenuation. Nakagami parametric imaging (NPI) based on the m parameter, which is related to the statistical property of echo envelope, is implemented to suppress contrast attenuation. Flow velocity (FV) and volumetric flow rate (VFR) are estimated through the least square fitting of burst depletion kinetic model to time m parameter curves (TMCs). A non-recirculating flow phantom is imaged as contrast microbubbles are infused at 10, 15, 20, 25, and 30 mL/min. Contrast microbubbles with two different concentrations are used to generate variations of contrast microbubble attenuation. The results suggest that 4 × 4 mm² is the optimal size of a sliding window of NPI for flow quantification under current experiment condition. At a lower microbubble concentration, the FV calculated from TMCs correlates strongly with actual FV in both unattenuated (R² = 0.97; p < 0.01) and attenuated regions (R² = 0.92; p < 0.01) within phantom. And there is a strong correlation (R² = 0.98; p < 0.01; slope = 0.96; intercept = 0.68) between VFR calculated from TMCs and actual VFR within the whole phantom. Similar results are obtained at higher microbubble concentrations. Compared with conventional ultrasound imaging that is intensity dependent, NPI achieves better performance on flow quantification in the presence of contrast microbubble attenuation.     

Imaging of Cardiac Autonomic Innervation with SPECT and PET

Heart failure (HF) is a condition with high mortality and morbidity. A major component of HF pathophysiology is the body’s neurohormonal response that includes activation of the sympathetic nervous system. Imaging of cardiac sympathetic innervation with a radionuclide tracer, such as the extensively studied norepinephrine analogue ¹²³I-meta-iodiobenzylguanidine (¹²³I-mIBG), provides unique insights into a patient’s condition. Cardiac uptake of ¹²³I-mIBG, measured as a heart to mediastinal ratio (H/M), has consistently been shown to correlate with poor outcome and predisposition to cardiac arrhythmias independent of conventional clinical, laboratory, and heart function parameters. ¹²³I-mIBG imaging promises to help monitor a patient’s clinical course and response to therapy, and shows potential to improve patient selection for advanced therapies such as ICDs, LVADs, and transplant. Imaging regional abnormalities, although less studied, shows promise for more precisely identifying patients at risk for arrhythmias, and higher resolution PET tracers such as ¹¹C-HED and ¹⁸?F-LMI1195 show potential.     

Apoptotic PET Imaging of Rat Pulmonary Fibrosis with Small-Molecule Radiotracer

Molecular Imaging and Biology - The purpose of this study was to assess the potential utility of small-molecule apoptotic radiotracer, 2-(5-[18F]fluoropentyl)-2-methyl malonic acid ([18F]ML-10),...     

Image-Based 2D Re-Projection for Attenuation Substitution in PET Neuroimaging

Purpose

In dual modality positron emission tomography (PET)/magnetic resonance imaging (MRI), attenuation correction (AC) methods are continually improving. Although a new AC can sometimes be generated from existing MR data, its application requires a new reconstruction. We evaluate an approximate 2D projection method that allows offline image-based reprocessing.

Procedure

2-Deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) brain scans were acquired (Siemens HR+) for six subjects. Attenuation data were obtained using the scanner’s transmission source (SAC). Additional scanning was performed on a Siemens mMR including production of a Dixon-based MR AC (MRAC). The MRAC was imported to the HR+ and the PET data were reconstructed twice: once using native SAC (ground truth); once using the imported MRAC (imperfect AC). The re-projection method was implemented as follows. The MRAC PET was forward projected to approximately reproduce attenuation-corrected sinograms. The SAC and MRAC images were forward projected and converted to attenuation-correction factors (ACFs). The MRAC ACFs were removed from the MRAC PET sinograms by division; the SAC ACFs were applied by multiplication. The regenerated sinograms were reconstructed by filtered back projection to produce images (SUBAC PET) in which SAC has been substituted for MRAC. Ideally SUBAC PET should match SAC PET. Via coregistered T1 images, FreeSurfer (FS; MGH, Boston) was used to define a set of cortical gray matter regions of interest. Regional activity concentrations were extracted for SAC PET, MRAC PET, and SUBAC PET.

Results

SUBAC PET showed substantially smaller root mean square error than MRAC PET with averaged values of 1.5 % versus 8.1 %.

Conclusions

Re-projection is a viable image-based method for the application of an alternate attenuation correction in neuroimaging.

     

Longitudinal PET Imaging of Doxorubicin-Induced Cell Death with 18F-Annexin V

Purpose

This study aims to apply longitudinal positron emission tomography (PET) imaging with ¹⁸?F-Annexin V to visualize and evaluate cell death induced by doxorubicin in a human head and neck squamous cell cancer UM-SCC-22B tumor xenograft model.

Procedures

In vitro toxicity of doxorubicin to UM-SCC-22B cells was determined by a colorimetric assay. Recombinant human Annexin V protein was expressed and purified. The protein was labeled with fluorescein isothiocyanate for fluorescence staining and ¹⁸?F for PET imaging. Established UM-SCC-22B tumors in nude mice were treated with two doses of doxorubicin (10?mg/kg each dose) with 1?day interval. Longitudinal ¹⁸?F-Annexin V PET was performed at 6?h, 24?h, 3?days, and 7?days after the treatment started. Following PET imaging, direct tissue biodistribution study was performed to confirm the accuracy of PET quantification.

Results

Two doses of doxorubicin effectively inhibited the growth of UM-SCC-22B tumors by inducing cell death including apoptosis. The cell death was clearly visualized by ¹⁸?F-Annexin V PET. The peak tumor uptake, which was observed at day 3 after treatment started, was significantly higher than that in the untreated tumors (1.56?±?0.23 vs. 0.89?±?0.31%ID/g, p?<?0.05). Moreover, the tumor uptake could be blocked by co-injection of excess amount of unlabeled Annexin V protein. At day 7 after treatment, the tumor uptake of ¹⁸?F-Annexin had returned to baseline level.

Conclusions

¹⁸?F-Annexin V PET imaging is sensitive enough to allow visualization of doxorubicin-induced cell death in UM-SCC-22B xenograft model. The longitudinal imaging with ¹⁸?F-Annexin will be helpful to monitor early response to chemotherapeutic anti-cancer drugs.