Brain and blood biomarkers of tauopathy and neuronal injury in humans and rats with neurobehavioral syndromes following blast exposure.

Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [18F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [18F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [18F]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI.

Evaluation of diabetic foot infection in nuclear medicine.

Diabetic foot infection is not only the most common cause of hospitalization among diabetic patients, but is also associated with high morbidity, mortality and major utilization of the resources. Managing diabetic patients with suspected foot infection is highly dependent on an early and accurate determination of its presence and location. Medical imaging is often used in the workup of these patients, as clinical diagnosis of osteomyelitis is often difficult, and invasive bone biopsy is infrequently used due to many limitations. In this article, we review the role and accuracy of commonly used medical imaging modalities in the evaluation of diabetic patients with suspected foot infection including osteomyelitis with particular emphasis on molecular nuclear medicine imaging. The impact of imaging on patients' management is also discussed. We finally comment on possible future directions in hybrid molecular imaging techniques.

Comparison of MR-based attenuation correction and CT-based attenuation correction of whole-body PET/MR imaging.

PURPOSE: The objective of this study was to evaluate the performance of the built-in MR-based attenuation correction (MRAC) included in the combined whole-body Ingenuity TF PET/MR scanner and compare it to the performance of CT-based attenuation correction (CTAC) as the gold standard. METHODS: Included in the study were 26 patients who underwent clinical whole-body FDG PET/CT imaging and subsequently PET/MR imaging (mean delay 100 min). Patients were separated into two groups: the alpha group (14 patients) without MR coils during PET/MR imaging and the beta group (12 patients) with MR coils present (neurovascular, spine, cardiac and torso coils). All images were coregistered to the same space (PET/MR). The two PET images from PET/MR reconstructed using MRAC and CTAC were compared by voxel-based and region-based methods (with ten regions of interest, ROIs). Lesions were also compared by an experienced clinician. RESULTS: Body mass index and lung density showed significant differences between the alpha and beta groups. Right and left lung densities were also significantly different within each group. The percentage differences in uptake values using MRAC in relation to those using CTAC were greater in the beta group than in the alpha group (alpha group -0.2 ± 33.6%, R(2) = 0.98, p < 0.001; beta group 10.31 ± 69.86%, R(2) = 0.97, p < 0.001). CONCLUSION: In comparison to CTAC, MRAC led to underestimation of the PET values by less than 10% on average, although some ROIs and lesions did differ by more (including the spine, lung and heart). The beta group (imaged with coils present) showed increased overall PET quantification as well as increased variability compared to the alpha group (imaged without coils). PET data reconstructed with MRAC and CTAC showed some differences, mostly in relation to air pockets, metallic implants and attenuation differences in large bone areas (such as the pelvis and spine) due to the segmentation limitation of the MRAC method.

Tumour-to-normal tissue (T/N) dosimetry ratios role in assessment of 90Y selective internal radiation therapy (SIRT).

OBJECTIVE: The purpose of our work is to assess the role of tumour-to-normal tissue (T/N) dosimetry ratios for predicting response in patients undergoing locoregional therapy to the liver with 90Y microspheres. METHODS: A total of 39 patients (7 female:32 male, mean age 68.3 ± 7.6 years), underwent positron emission tomography (PET)/CT imaging after treatment with 90Y microspheres. For attenuation correction and localization of the 90Y microspheres, the low-dose, non-diagnostic CT images from PET/CT were used. The acquisition took 15 min and the reconstruction matrix size was 200 × 200 × 75 mm and voxel size of 4.07 × 4.07 × 3.00 mm. For dosimetry calculations, the local deposition method with known activity of 90Y was used. For each patient, regions of interest for tumour(s) and whole liver were manually created; the normal tissue region of interest was created automatically. mRECIST criteria on MRI done at 1 month post-treatment and subsequently every 3 months after 90Y treatment, were used to assess response. RESULTS: For 39 patients, the mean liver, tumour and normal tissue doses (mean ± SD) were, 55.17 ± 26.04 Gy, 911.87 ± 866.54 Gy and 47.79 ± 20.47 Gy, respectively. Among these patients, 31 (79%) showed complete response (CR) and 8 (21%) showed progression of disease (PD). For patients with CR, the mean T/N dose ratio obtained was 24.91 (range 3.09-80.12) and for patients with PD, the mean T/N dose ratio was significantly lower, at 6.69 (range 0.36-14.75). CONCLUSION: Our data show that patients with CR have a statistically higher T/N dose ratio than those with PD. Because, the number of PD cases was limited and partial volume effect was not considered, further investigation is warranted. ADVANCES IN KNOWLEDGE: T/N dosimetry ratios can be used for assessing response in patients undergoing locoregional therapy to the liver with 90Y microspheres.

Radiation segmentectomy for curative intent of unresectable very early to early stage hepatocellular carcinoma (RASER): a single-centre, single-arm study.

BACKGROUND: Unresectable solitary very early to early stage hepatocellular carcinoma is managed with ablation for curative intent. Radiation segmentectomy is a treatment option that delivers radioactive 90yttrium (90Y)-bound microspheres transarterially to a segment of liver. The aim of this study was to assess the safety and efficacy of radiation segmentectomy in patients with unresectable hepatocellular carcinoma deemed unfavourable for ablation. METHODS: RASER was a single-centre, single-arm study that included adults (>18 years) with solitary hepatocellular carcinoma with unfavourable location for ablation, without metastasis or macrovascular invasion. Eligibility criteria included measurable disease 3 cm or less in diameter, Child-Pugh score A-B7, an Eastern Cooperative Oncology Group score of 0, and adequate haematological and organ function. The primary endpoint was target tumour response measured by mRECIST. Patients were followed up with imaging and office visits for up to 24 months. The trial is registered with ClinicalTrials.gov (NCT03248375), and is completed. FINDINGS: Individuals were enrolled between Aug 3, 2016, and April 4, 2019, and the last patient follow-up occurred on March 31, 2021. Of the 44 individuals assessed for eligibility, 29 patients were included in the study. Initial target lesion complete response was observed in 24 (83%) of 29 patients, and partial response was observed in five (17%) of patients. All patients had an initial objective response and 26 (90%) individuals had a sustained complete response. Four (14%) patients had grade 3 leukopenia and two (7%) had grade 3 thrombocytopenia. There were two (7%) non-laboratory-related grade 3 adverse events (one arterial injury and one ascites). The most frequent (>10% patients) grade 1 or 2 adverse events were fatigue (nine [31%]); nausea, vomiting, or anorexia (seven [24%]); abdominal discomfort (six [21%]), leukopenia (nine [31%]), thrombocytopenia (four [14%]), increased alkaline phosphatase (four [14%]), increased alanine or aspartate aminotransferase (four [14%]), increased bilirubin (four [14%]), and decreased albumin (six [21%]). There was one death that was not treatment related. INTERPRETATION: Radiation segmentectomy was efficacious, with a low proportion of high-grade adverse events in patients with unresectable very early to early stage hepatocellular carcinoma with suboptimal location for ablation. These results suggest that radiation segmentectomy should be further investigated as a potential curative treatment option for well selected patients. FUNDING: Boston Scientific.

An estimate of 90Y dosimetry for bremsstrahlung SPECT/CT imaging in liver therapy with 90Y microspheres.

OBJECTIVE: Bremsstrahlung SPECT/CT (bSPECT/CT) is one of the most common methods for post-therapy imaging in 90Y microspheres selective internal radiation therapy (SIRT) of liver cancers. Here, we are proposing a simple approach using bSPECT/CT to estimate mean absorbed dose to the liver in patients undergoing treatment with 90Y microspheres. MATERIALS AND METHODS: In our previous study comparing 90Y dosimetry obtained using bSPECT/CT vs PET/CT, we found that there was a large difference between the mean absorbed dose values to the whole-liver. However, there was a high linear correlation between the doses, which presented an opportunity for quantitative assessment using bSPECT/CT 90Y imaging. In this study, after treatment with 90Y microspheres, 43 patients were immediately imaged on a dual-head Infinia SPECT/CT gamma camera and on a mCT PET/CT system. Images from 25 of the patients, randomly selected, were used to calculate the correlation of mean liver doses obtained from bSPECT/CT vs. PET/CT. For the remaining 18 patients, the calculated correlation was used to estimate doses obtained from bSPECT/CT, and these estimations were then compared to the doses obtained from PET/CT, considered the gold standard for quantitative analysis. RESULTS: From the 25 selected patients, the calculated linear correlation between bSPECT/CT and PET/CT 90Y mean absorbed doses in whole liver was high (r^2 = 0.97), with a slope of 2.80 and an intercept of -0.63. This linear fit was used to calculate the bSPECT/CT doses for the remaining 18 patients. For these patients, the mean whole-liver dose obtained from bSPECT/CT fitted data vs that obtained from PET/CT were 50.59 Gy and 50.81 Gy, respectively. The average dose difference was 0.2 ± 5.4 Gy (range -18.2%-13.0%). The repeatability coefficient was 10.5 (20.8 % of the mean). CONCLUSION: Although quantitative bremsstrahlung imaging is difficult, it is possible to calculate adequate estimates of whole-liver dosimetry from bSPECT/CT imaging that is calibrated using its correlation with post-therapy PET/CT 90Y images.

Comparison of posttherapy 90Y positron emission tomography/computed tomography dosimetry methods in liver therapy with 90Y microspheres.

The aim of our study was to compare dosimetry methods for yttrium-90 (90Y) positron emission tomography/computed tomography (PET/CT). Twenty-five patients were taken to a PET/CT suite following therapy with 90Y microspheres. The low mA, nondiagnostic CT images were used for attenuation correction and localization of the 90Y microspheres. The acquisition time was 15 min, the reconstruction matrix size was 200 mm × 200 mm × 75 mm, and voxel size was 4.07 mm × 4.07 mm × 3.00 mm. Two software packages, MIM 6.8 and Planet Dose, were utilized to calculate 90Y dosimetry. Three methods were used for voxel-based dosimetry calculations: the local deposition method (LDM), LDM with scaling (LDMwS) for known injected activity, and a dose point kernel (DPK) method using the MIRD kernel. Only the DPK approach was applied to the Planet Dose software. LDM and LDMwS were only applied to the MIM software. The average total liver dosimetry values (mean ± standard deviation) were 60.93 ± 28.62 Gy, 53.59 ± 23.47 Gy, 55.33 ± 24.80 Gy, and 54.25 ± 23.70 Gy for LDMwS, LDM, DPK with MIM, and DPK with Planet Dose (DOSI), respectively. In most cases, the LDMwS method produced slightly higher dosimetry values than the other methods. The MIM and Planet Dose DPK dosimetry values (i.e., DPK vs. DOSI) were highly comparable. Bland-Altman analysis calculated a mean difference of 1.1 ± 2.2 Gy. The repeatability coefficient was 4.4 (7.9% of the mean). The MIM and Planet Dose DPK dosimetry values were practically interchangeable. 90Y dosimetry values obtained by all methods were similar, but LDMwS tended to produce slightly higher values.

Fluoro-deoxy-glucose positron emission tomography for evaluation of indeterminate lung nodules: assigning a probability of malignancy may be preferable to binary readings.

OBJECTIVE: To assess the diagnostic value of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) using standard uptake values (SUV) in the differential diagnoses of indeterminate pulmonary nodules. Specifically, we assessed the probability of malignancy for various SUV ranges, and compared the diagnostic efficacy of SUV with and without correction for partial volume effects on the basis of lesion size. METHODS: The FDG-PET scans performed on 158 patients with biopsy-proven pulmonary lesions seen on computed tomography (CT) scan were retrospectively reviewed. Histopathological confirmation was obtained to establish the diagnosis of the lesions. A region of interest (ROI) was drawn for each lesion, and FDG uptake was quantified (SUV(raw)). The SUV(raw) values were normalized for the "size" of the pulmonary lesions measured on CT (SUV(size)). Sensitivity and specificity of FDG-PET for pulmonary lesions <2 cm in diameter or > or =2 cm in diameter were determined at SUV cutoff values of 2.5. The areas under the receiver-operating characteristic (ROC) curve for SUV(raw) and SUV(size) regarding the presence of malignancy were compared for statistical differences. The frequency of malignant lesions for each range of SUVs was obtained to produce the probability of cancer (POC). RESULTS: The mean SUV(raw) was 3.17 +/- 2.76 and 9.18 +/- 6.72 for benign and malignant lesions, respectively. When a SUV(raw) value of 2.5 was used as a cutoff, sensitivity and specificity were 89% and 51%, respectively, for all lesion sizes. The sensitivity and specificity at a cutoff SUV(raw) of 2.5 for lesions less than 2 cm in diameter were 75% and 72%, respectively, and 92% and 41% for lesions 2 cm or greater, respectively. The sensitivity and specificity at a cutoff SUV(size) of 2.5 were 88% and 42%, respectively. The area under the ROC curves for SUV(raw) and SUV(size) was 0.816 and 0.743, respectively (P value 0.034). When the SUV(raw) was divided into three groups, the probability of malignancy was 26% when the SUV(raw) was <2, 57% for 2 < or = SUV(raw) < 6, and 89% for SUV(raw) > or = 6. CONCLUSIONS: The FDG-PET is a reasonably accurate and useful tool for characterizing the nature of indeterminate pulmonary lesions, although the specificity was not as high as that reported in the literature, probably owing in part to our patient population and selection bias. Our data suggest that reporting the results of PET studies as a probability rather than as positive or negative for malignancy would be more useful for further management decision making. Correction of SUVs for tumor size did not improve accuracy.

Comparison of Standardized Uptake Value Ratio Calculations in Amyloid Positron Emission Tomography Brain Imaging.

Amyloid positron emission tomography (PET) imaging with florbetapir 18F (18F-AV-45) allows in vivo assessment of cerebral amyloid load and can be used in the evaluation of progression of Alzheimer's disease (AD) and other dementias associated with b-amyloid. However, cortical amyloid deposition can occur in healthy cases, as well as in patients with AD and quantification of cortical amyloid burden can improve the 18F-AV-45 PET imaging evaluations. The quantification is mostly performed by cortical-to-cerebellum standardized uptake value ratio (SUVr). The aim of our study was to compare two methods for SUVr calculations in amyloid florbetapir 18F PET brain imaging. In amyloid florbetapir 18F PET brain imaging study, we imaged 42 cases with the mean age of 72.6 ± 9.9 (mean ± standard deviation). They were imaged on different PET/computed tomography systems with 369.0 ± 34.2 kBq of 18F florbetapir. Data were reconstructed using the vendor's reconstruction software. Corresponding magnetic resonance imaging (MRI) data were retrieved, and matched PET and MRI data were transferred to a common platform. Two methods were used for the calculation of the ratio of cortical-to-cerebellar signal (SUVr). One method was based on the MIM Software Inc., Version 6.4 software and only uses PET data. The second approach used the PMOD Neuro tool (version 3.5). This approach utilizes PET and corresponding MRI data (preferably T1-weighted) for better brain segmentation. For all the 42 cases, the average SUVr values for MIM and PMOD applications were 1.24 ± 0.26 and 1.22 ± 0.25, respectively, with a mean difference of 0.02 ± 0.15. The repeatability coefficient was 0.15 (12.3% of the mean). The Spearman's rank correlation coefficient was very high, r = 0.96. For amyloid-negative cases, the average SUVr values were lower than all group SUVr average values, 0.96 ± 0.07 and 1.00 ± 0.09, for MIM and PMOD applications, respectively. A mean difference was 0.04 ± 0.12, the repeatability coefficient was 0.12 (12.9% of the mean) and the Spearman's rank correlation coefficient was modest, r = 0.55. For amyloid-positive patients, the average SUVr values were higher than the same all group values, 1.34 ± 0.16 and 1.35 ± 0.20, respectively, with a mean difference of 0.01 ± 0.16. The repeatability coefficient was 0.16 (11.9% of the mean). The Spearman's rank correlation coefficient was high, r = 0.93. Our results indicated that the SUVr values derived using MIM and PMOD Neuro are effectively interchangeable and well correlated. However, PET template-based quantification (MIM approach) is clinically friendlier and easier to use. MRI template-based quantification (PMOD Neuro) better delineates different regions of the brain, can be used with any tracer, and therefore is more suitable for research.

Comparison of PET/CT and PET/MR imaging and dosimetry of yttrium-90 (90Y) in patients with unresectable hepatic tumors who have received intra-arterial radioembolization therapy with 90Y microspheres.

BACKGROUND: The aim of our study was to compare 90Y dosimetry obtained from PET/MRI versus PET/CT post-therapy imaging among patients with primary or metastatic hepatic tumors. First, a water-filled Jaszczak phantom containing fillable sphere with 90Y-chloride was acquired on both the PET/CT and PET/MRI systems, in order to check the cross-calibration of the modalities. Following selective internal radiation therapy (SIRT) with 90Y microspheres, 32 patients were imaged on a PET/CT system, immediately followed by a PET/MRI study. Reconstructed images were transferred to a common platform and used to calculate 90Y dosimetry. A Passing-Bablok regression scatter diagram and the Bland and Altman method were used to analyze the difference between the dosimetry values. RESULTS: The phantom study showed that both modalities were calibrated with less than 1% error. The mean liver doses for the 32 subjects calculated from PET/CT and PET/MRI were 51.6 ± 24.7 Gy and 46.5 ± 22.7 Gy, respectively, with a mean difference of 5.1 ± 5.0 Gy. The repeatability coefficient was 9.0 (18.5% of the mean). The Spearman rank correlation coefficient was very high, ρ = 0.97. Although the maximum dose to the liver can be significantly different (up to 40%), mean liver doses from each modalities were relatively close, with a difference of 18.5% or less. CONCLUSIONS: The two main contributors to the difference in 90Y dosimetry calculations using PET/CT versus PET/MRI can be attributed to the differences in regions of interest (ROIs) and differences attributed to attenuation correction. Due to the superior soft-tissue contrast of MRI, liver contours are usually better seen than in CT images. However, PET/CT provides better quantification of PET images, due to better attenuation correction. In spite of these differences, our results demonstrate that the dosimetry values obtained from PET/MRI and PET/CT in post-therapy 90Y studies were similar.

Quantitative comparison of pre-therapy 99mTc-macroaggregated albumin SPECT/CT and post-therapy PET/MR studies of patients who have received intra-arterial radioembolization therapy with 90Y microspheres.

OBJECTIVE: The aim of our study was to compare yttrium -90 (90Y) dosimetry obtained from pre-therapy 99mTc-macroaggregated albumin (MAA) SPECT/CT versus post-therapy PET/MRI imaging among patients with primary or metastatic hepatic tumors. MATERIALS AND METHODS: Prior to 90Y radioembolization (RE), 32 patients underwent a scan using MAA mimicking 90Y distribution. After RE with 90Y microspheres, the patients were imaged on a PET/MRI system. Reconstructed images were transferred to a common platform and used to calculate 90Y dosimetry. The Passing-Bablok regression scatter diagram and the Bland and Altman method were used to analyze the difference between dosimetry values. RESULTS: For MAA and PET/MRI modalities, the mean liver doses for all 32 subjects were 43.0 ±â€¯20.9 Gy and 46.5 ±â€¯22.7 Gy, respectively, with a mean difference of 3.4 ±â€¯6.2 Gy. The repeatibility coefficient was 12.1 (27.0% of the mean). The Spearman rank correlation coefficient was high (ρ = 0.92). Although, there was a substantial difference in the maximum doses to the liver between the modalities, the mean liver doses were relatively close, with a difference of 24.0% or less. CONCLUSIONS: The two main contributors to the difference between dosimetry calculations using MAA versus 90Y PET/MRI can be attributed to the changes in catheter positioning as well as the liver ROIs used for the calculations. In spite of these differences, our results demonstrate that the dosimetry values obtained from pre-therapy MAA SPECT/CT scans and PET/MRI post-therapy 90Y studies were not significantly different.

Multi institutional quantitative phantom study of yttrium-90 PET in PET/MRI: the MR-QUEST study.

BACKGROUND: Yttrium-90 (90Y) radioembolization involves the intra-arterial delivery of radioactive microspheres to treat hepatic malignancies. Though this therapy involves careful pre-treatment planning and imaging, little is known about the precise location of the microspheres once they are administered. Recently, there has been growing interest post-radioembolization imaging using positron-emission tomography (PET) for quantitative dosimetry and identifying lesions that may benefit from additional salvage therapy. In this study, we aim to measure the inter-center variability of 90Y PET measurements as measured on PET/MRI in preparation for a multi-institutional prospective phase I/II clinical trial. Eight institutions participated in this study and followed a standardized phantom filling and imaging protocol. The NEMA NU2-2012 body phantom was filled with 3 GBq of 90Y chloride solution. The phantom was imaged for 30 min in listmode on a Siemens Biograph mMR non-TOF PET/MRI scanner at five time points across 10 days (0.3-3.0 GBq). Raw PET data were sent to a central site for image reconstruction and data analysis. Images were reconstructed with optimal parameters determined from a previous study. Volumes of interest (VOIs) matching the known sphere diameters were drawn on the vendor-provided attenuation map and propagated to the PET images. Recovery coefficients (RCs) and coefficient of variation of the RCs (COV) were calculated from these VOIs for each sphere size and activity level. RESULTS: Mean RCs ranged from 14.5 to 75.4%, with the lowest mean RC coming from the smallest sphere (10 mm) on the last day of imaging (0.16 MBq/ml) and the highest mean RC coming from the largest sphere (37 mm) on the first day of imaging (2.16 MBq/ml). The smaller spheres tended to exhibit higher COVs. In contrast, the larger spheres tended to exhibit lower COVs. COVs from the 37 mm sphere were < 25.3% in all scans. For scans with ≥ 0.60 MBq/ml, COVs were ≤ 25% in spheres ≥ 22 mm. However, for all other spheres sizes and activity levels, COVs were usually > 25%. CONCLUSIONS: Post-radioembolization dosimetry of lesions or other VOIs ≥ 22 mm in diameter can be consistently obtained (< 25% variability) at a multi-institutional level using PET/MRI for any clinically significant activity for 90Y radioembolization.

Optimization of yttrium-90 PET for simultaneous PET/MR imaging: A phantom study.

PURPOSE: Positron emission tomography (PET) imaging of yttrium-90 in the liver post radioembolization has been shown useful for personalized dosimetry calculations and evaluation of extrahepatic deposition. The purpose of this study was to quantify the benefits of several MR-based data correction approaches offered by using a combined PET/MR system to improve Y-90 PET imaging. In particular, the feasibility of motion and partial volume corrections were investigated in a controlled phantom study. METHODS: The ACR phantom was filled with an initial concentration of 8 GBq of Y-90 solution resulting in a contrast of 10:1 between the hot cylinders and the background. Y-90 PET motion correction through motion estimates from MR navigators was evaluated by using a custom-built motion stage that simulated realistic amplitudes of respiration-induced liver motion. Finally, the feasibility of an MR-based partial volume correction method was evaluated using a wavelet decomposition approach. RESULTS: Motion resulted in a large (∼40%) loss of contrast recovery for the 8 mm cylinder in the phantom, but was corrected for after MR-based motion correction was applied. Partial volume correction improved contrast recovery by 13% for the 8 mm cylinder. CONCLUSIONS: MR-based data correction improves Y-90 PET imaging on simultaneous PET/MR systems. Assessment of these methods must be studied further in the clinical setting.

Improving 3D PET imaging by restoration: a phantom study.

The main objective of our work is to improve 3D PET imaging. Compared with 2D PET, 3D PET imaging has slightly worse axial resolution and a significantly higher contribution of scatter and randoms, but 3D PET has much better sensitivity than 2D PET imaging. A Jaszczak deluxe phantom was acquired in 3D mode on our GE Advance PET system. Activity of 333 MBq of 18F was uniformly distributed. Prior to the emission scan, blank and transmission scans had been acquired. They were used for attenuation correction. The duration of the emission scan was 20 min, transmission 10 min, and blank 20 min. Standard FBP reconstruction software provided by the vendor was used to obtain slice images. Point spread function was also acquired in a 21 cm diameter cylinder phantom filled with water 6.0 cm from the center and used to create restoration filters. Two restoration filters were applied, medium and sharp. Results showed significant improvement in resolution, contrast and detectability of the cold rods. The artifacts outside the phantom were also significantly reduced. For 11.1 mm rods, average contrast was 0.49+/-0.02 in the original image, 0.52+/-0.04 in the medium restored image, and in the sharply restored image 0.75+/-0.05. For 7.9 mm rods, average contrast was 0.07+/-0.01 in the original image, 0.21+/-0.03 in the medium restored image, and 0.50+/-0.04 in the sharply restored image. The amount of noise in the uniform slices, measured as the coefficient of variation (COV), was 5.5, 7.1 and 10.8% in the original image and in the images restored with medium and sharp filters, respectively. In conclusion, restoration can significantly improve the resolution and contrast of 3D PET imaging.

Improving (18)F-Fluoro-D-Glucose-Positron Emission Tomography/Computed Tomography Imaging in Alzheimer's Disease Studies.

The goal was to improve Alzheimer's 2-deoxy-2-(18)F-fluoro-D-glucose ((18)F FDG)-positron emission tomography (PET)/computed tomography (CT) imaging through application of a novel, hybrid Fourier-wavelet windowed Fourier transform (WFT) restoration technique, in order to provide earlier and more accurate clinical results. General Electric Medical Systems downward-looking sonar PET/CT 16 slice system was used to acquire studies. Patient data were acquired according the Alzheimer's disease Neuroimaging Initiative (ADNI) protocol. Here, we implemented Fourier-wavelet regularized restoration, with a Butterworth low-pass filter, order n = 6 and a cut-off frequency f = 0.35 cycles/pixel and wavelet (Daubechies, order 2) noise suppression. The original (PET-O) and restored (PET-R) ADNI subject PET images were compared using the Alzheimer's discrimination analysis by dedicated software. Forty-two PET/CT scans were used in the study. They were performed on eleven ADNI subjects at intervals of approximately 6 months. The final clinical diagnosis was used as a gold standard. For three subjects, the final clinical diagnosis was mild cognitive impairment and those 13 PET/CT studies were not included in the final comparison, as the result was considered as inconclusive. Using the reminding 29 PET/CT studies (23 AD and 6 normal), the sensitivity and specificity of the PET-O and PET-R were calculated. The sensitivity was 0.65 and 0.96 for PET-O and PET-R, respectively, and the specificity was 0.67 and 0.50 for PET-O and PET-R. The accuracy was 0.66 and 0.86 for PET-O and PET-R, respectively. The results of the study demonstrated that the accuracy of three-dimensional brain F-18 FDG PET images was significantly improved by Fourier-wavelet restoration filtering.

Comparison of 2-dimensional and 3-dimensional 82Rb myocardial perfusion PET imaging.

UNLABELLED: We compared 2-dimensional (2D) and 3-dimensional (3D) (82)Rb PET imaging in 3 different experiments: in a realistic heart-thorax phantom, in a uniformity-resolution phantom, and in 14 healthy volunteers. METHODS: A nonuniform heart-thorax phantom was filled with 111 MBq of (82)Rb injected into the left ventricular (LV) wall. In the LV wall of the cardiac phantom, 3 inserts-1, 2, and 3 cm in diameter-were placed to simulate infarcts. A standard rest cardiac PET imaging protocol in 2D and 3D modes was used. Following the same protocol, a uniformity-resolution phantom with uniformly distributed activity of 1,998 MBq and 740 MBq of (82)Rb in water was used to obtain 2D PET images and 3D PET images, respectively. All 2D volunteer studies were performed by injecting 2,220 MBq of (82)Rb intravenously. For half the volunteers, 3D studies were performed with a high dose (HD) (2,220 MBq) of (82)Rb; for the remainder of the 3D studies, a low dose (LD) (740 MBq) of (82)Rb was used. In the 2D and LD 3D studies, there was a delay of 2 min and 3 min, respectively, followed by a 6-min acquisition. In the HD 3D volunteer studies, there was a delay of 5 min followed by a 6-min acquisition. Circumferential profiles of the short-axis slices and the contrast of the inserts were used to evaluate the cardiac phantom PET images. The transaxial slices from the uniformity-resolution phantom were evaluated by visual inspection and by measuring uniformity. The human studies were evaluated by measuring the contrast between LV wall and LV cavity, using linear profiles and visual analysis. RESULTS: In the cardiac phantom study, circumferential profiles for the 2D and 3D images were similar. The contrast values for the 1-, 2-, and 3-cm inserts in the 2D study were 0.19 +/- 0.03, 0.34 +/- 0.05, and 0.61 +/- 0.03, respectively. The respective contrast values in the 3D study were 0.15 +/- 0.02, 0.36 +/- 0.04, and 0.52 +/- 0.05. In the uniformity-resolution phantom study, the coefficients of variation, calculated for a representative uniform slice, were 5.3% and 7.6% for the 2D and 3D studies, respectively. For the 7 volunteers on whom HD 3D was used, the mean 2D contrast was 0.33 +/- 0.08 and the mean HD 3D contrast was 0.35 +/- 0.08 (P = not statistically significant). For the other 7 volunteers, on whom LD 3D was used, the mean 2D contrast was 0.39 +/- 0.06 and the mean LD 3D contrast was 0.39 +/- 0.10 (P = not statistically significant). In the tomographic slices, the 2D and 3D images and polar plots were similar. CONCLUSION: When obtained with a PET system having a high counting-rate performance, 2D and 3D (82)Rb PET cardiac images are comparable. LD 3D imaging can make (82)Rb PET cardiac imaging more affordable.

Reducing exposure from 57Co sources during breast lymphoscintigraphy by optimizing energy windows and other suggested enhancements of acquisition and the display of images.

UNLABELLED: We set out to measure the reduction in exposure attained by using a weak 57Co sheet source with optimal energy windows. METHODS: Two groups of 10 lymphoscintigraphy studies were analyzed. Group 1 consisted of 10 studies obtained with a stronger source of 57Co, 59 MBq (1.6 mCi) at the time of data acquisition, with transmission images acquired at 3 energy windows of 115-129, 130-134, and 135-150 keV. Group 2 consisted of 10 studies with a weaker sheet source of 57Co, 11 MBq (0.3 mCi). Transmission images were acquired at 3 energy windows of 112-132, 130-134, and 135-150 keV. Same-sized regions of interest (ROIs) were drawn on the patient's torso (PT) and on the nonattenuated image of the transmission source itself (TS), all 1-min images. The counts in each ROI obtained over 1 min and the ratios between the TS ROI and the PT ROI were calculated for all of the energies. Dosimetry calculations based on measured exposure rates and the activity of the sheet sources were used to calculate the patient equivalent dose at 30 cm. RESULTS: For the 57Co energy window, group 1 had an average ROI count of 1,955 in the TS region and 135 counts in the PT region. The average ratio of TS/PT was 15.4. Similarly, group 2 had an average ROI count of 646.4 in the TS region and 91.2 counts in the PT region. The average ratio of TS/PT was 8.6. The relative "outlining performance," when comparing the 57Co and 99mTc windows, showed an average improvement when using the 57Co window of 4.4 and 5.8 times for group 1 and group 2, respectively (TS/PT at 57Co window)/(TS/PT at 99mTc window). Estimates of the patient equivalent dose per study were 2.30 microSv for the stronger 57Co flood source and 0.46 microSv for the weaker 57Co flood source, a 5-fold reduction in equivalent dose. Technologists received less than half of the above doses. CONCLUSION: Use of expanded, separate energy windows optimized for the primary 122-keV photon of 57Co greatly improves transmission scan image quality compared with the standard 140-keV 99mTc windows used for the delineation of the sentinel node. This markedly reduces exposure for all, by allowing the use of a weaker source, and can save time.

Quantitative comparison of yttrium-90 (90Y)-microspheres and technetium-99m (99mTc)-macroaggregated albumin SPECT images for planning 90Y therapy of liver cancer.

Yttrium-90 ((90)Y)-microspheres administered via the hepatic artery has been used for the treatment of unresectable primary or metastatic cancer in the liver. Prior to (90)Y therapy, however, the (90)Y administered activity and the percent shunting to lungs must be determined, most commonly by gamma camera imaging of technetium-99m ((99m)Tc)-macroaggregated albumin (MAA). The purpose of the current study was to identify and evaluate an objective measure of the correlation of (90)Y and MAA activity distributions and thus assess the reliability of MAA imaging for evaluation of (90)Y administered activity and tumor and liver radiation doses. The MAA study consisted of two acquisitions. After administration of 185 MBq of MAA, a partial-body or so-called breakthrough scan was performed in order to determine the percent shunting to lungs. Immediately after a breakthrough scan, a combined single-photon emission computed tomography (SPECT)/transmission computed tomography (CT) scanner was used to image MAA distribution in order to derived the prescribed (90)Y administered activity based on tumor and liver dosimetry. (90)Y SPECT/CT was performed 2-4 weeks later and activities used were in the range of 777-2,442 MBq. In order to compare (90)Y and MAA SPECT images, first the respective CT image sets were registered using a transform based on normalized mutual information. The transform thus derived was used to align the 90Y and MAA SPECT image sets, and the Spearman's (rho) rank correlation as well as image distance (L2-norm) between the registered SPECT images were then calculated. The Spearman's rank correlation values ranged from 0.451 to 0.818 and the L2 distances from 0.626 to 2.889. Based on visual inspection, the registration of the (90)Y and MAA SPECT images appeared reasonably accurate. The regression coefficient (r) between visual scoring and the Spearman's rank correlation was 0.65 and between visual scoring and L2 distance 0.61. The Spearman's rank correlation thus appears to be more reliable than the image distance for assessing the correlation of the (90)Y and MAA images.

Repeatability of regional myocardial blood flow calculation in 82Rb PET imaging.

BACKGROUND: We evaluated the repeatability of the calculation of myocardial blood flow (MBF) at rest and pharmacological stress, and calculated the coronary flow reserve (CFR) utilizing 82Rb PET imaging. The aim of the research was to prove high repeatability for global MBF and CFR values and good repeatability for regional MBF and CFR values. The results will have significant impact on cardiac PET imaging in terms of making it more affordable and increasing its use. METHODS: 12 normal volunteers were imaged at rest and during pharmacological stress, with 2220 MBq of 82Rb each. A GE Advance PET system was used to acquire dynamic 50-frame studies. MBF was calculated with a 2-compartmental model using a modified PMOD program (PMOD; University Hospital Zurich, Zurich, Switzerland). Two differential equations, describing a 2-compartmental model, were solved by numerical integration and using Levenberg-Marquardt's method for fitting data. The PMOD program defines 16 standard segments and calculates myocardial flow for each segment, as well as average septal, anterior, lateral, inferior and global flow. Repeatability was evaluated according to the method of Bland and Altman. RESULTS: Global rest and stress MBF, as well as global CFR, showed very good repeatability. No significant differences were found between the paired resting global MBF (0.63 +/- 0.13 vs. 0.64 +/- 0.13 mL/min/g; mean difference, -1.0% +/- 2.6%) and the stress global MBF (1.37 +/- 0.23 vs. 1.37 +/- 0.24; mean difference, 0.1% +/- 2.3%). Global CFR was highly reproducible (2.25 +/- 0.56 vs. 2.22 +/- 0.54, P = not statistically significant; mean difference, 1.3% +/- 14.3%). Repeatability coefficients for global rest MBF were 0.033 (5.2%) and stress MBF 0.062 (4.5%) mL/min/g. Regional rest and stress MBF and CFR have shown good reproducibility. The average per sector repeatability coefficients for rest MBF were 0.056 (8.5%) and stress MBF 0.089 (6.3%) mL/min/g, and average repeatability coefficient for CFR was 0.25 (10.6%). CONCLUSION: The results of the study show that software calculation of MBF and CFR with 82Rb myocardial PET imaging is highly repeatable for global values and has good repeatability for regional values.