Comparison of maximum likelihood and conventional PET scatter scaling methods for 18 F-FDG and 68 Ga-DOTATATE PET/CT.

PURPOSE: We aim to quantify differences between a new maximum likelihood (ML) background scaling (MLBS) algorithm and two conventional scatter scaling methods for clinical PET/CT. A common source of reduced image quantification with conventional scatter corrections is attributed to erroneous scaling of the initial scatter estimate to match acquired scattered events in the sinogram. MLBS may have performance advantages over conventional methods by using all available data intersecting the subject. METHODS: A retrospective analysis was performed on subjects injected with 18 F-FDG (N = 71) and 68 Ga-DOTATATE (N = 11) and imaged using time-of-flight (TOF) PET/CT. The scatter distribution was estimated with single scatter simulation approaches. Conventional scaling algorithms included (a) tail fitted background scaling (TFBS), which scales the scatter to "tails" outside the emission support, and (b) absolute scatter correction (ABS), which utilizes the simulated scatter distribution with no scaling applied. MLBS consisted of an alternating iterative reconstruction with a TOF-based ML activity image update allowing negative values (NEG-ML) and nested loop ML scatter scaling estimation. Scatter corrections were compared using reconstructed images as follows: (a) normalized relative difference images were generated and used for voxel-wise analysis, (b) liver and suspected lesion ROIs were drawn to compute mean SUVs, and (c) a qualitative analysis of overall diagnostic image quality, impact of artifacts, and lesion conspicuity was performed. Absolute quantification and normalized relative differences were also assessed with an 18 F-FDG phantom study. RESULTS: For human subjects 18 F-FDG data, Bland-Altman plots demonstrated that the largest normalized voxel-wise differences were observed close to the lower limit (SUV = 1.0). MLBS reconstructions trended towards higher scatter fractions compared to TFBS and ABS images, with median voxel differences across all subjects for TFBS-MLBS measured at 1.7% and 7.6% for 18 F-FDG and 68 Ga-DOTATATE, respectively. For mean SUV analysis, there was a high degree of correlation between the scatter corrections. For 18 F-FDG, ABS scatter correction reconstructions trended towards higher liver mean SUVs relative to MLBS. The qualitative image analysis revealed no significant differences between TFBS and MLBS image reconstructions. For a uniformly filled relatively large 37 cm diameter phantom, MLBS produced the lowest bias in absolute quantification, while normalized voxel-wise differences showed a trend in scatter correction performance consistent with the human subjects study. CONCLUSIONS: For 18 F-FDG, MLBS is at least a valid substitute to TFBS, providing reconstructed image performance comparable to TFBS in most subjects but exhibiting quantitative differences in cases where TFBS is typically prone to inaccuracies (e.g., due to patient motion and CT-based attenuation map truncation). Particularly for low contrast regions, quantification differs for ABS compared to MLBS and TFBS, and caution should be taken when utilizing ABS for decision-making based on quantitative metrics.

Evaluation of MLACF based calculated attenuation brain PET imaging for FDG patient studies.

Calculating attenuation correction for brain PET imaging rather than using CT presents opportunities for low radiation dose applications such as pediatric imaging and serial scans to monitor disease progression. Our goal is to evaluate the iterative time-of-flight based maximum-likelihood activity and attenuation correction factors estimation (MLACF) method for clinical FDG brain PET imaging. FDG PET/CT brain studies were performed in 57 patients using the Biograph mCT (Siemens) four-ring scanner. The time-of-flight PET sinograms were acquired using the standard clinical protocol consisting of a CT scan followed by 10 min of single-bed PET acquisition. Images were reconstructed using CT-based attenuation correction (CTAC) and used as a gold standard for comparison. Two methods were compared with respect to CTAC: a calculated brain attenuation correction (CBAC) and MLACF based PET reconstruction. Plane-by-plane scaling was performed for MLACF images in order to fix the variable axial scaling observed. The noise structure of the MLACF images was different compared to those obtained using CTAC and the reconstruction required a higher number of iterations to obtain comparable image quality. To analyze the pooled data, each dataset was registered to a standard template and standard regions of interest were extracted. An SUVr analysis of the brain regions of interest showed that CBAC and MLACF were each well correlated with CTAC SUVrs. A plane-by-plane error analysis indicated that there were local differences for both CBAC and MLACF images with respect to CTAC. Mean relative error in the standard regions of interest was less than 5% for both methods and the mean absolute relative errors for both methods were similar (3.4% ± 3.1% for CBAC and 3.5% ± 3.1% for MLACF). However, the MLACF method recovered activity adjoining the frontal sinus regions more accurately than CBAC method. The use of plane-by-plane scaling of MLACF images was found to be a crucial step in order to obtain improved activity estimates. Presence of local errors in both MLACF and CBAC based reconstructions would require the use of a normal database for clinical assessment. However, further work is required in order to assess the clinical advantage of MLACF over CBAC based method.

Noninvasive assessment of myocardial viability in a small animal model: comparison of MRI, SPECT, and PET.

Acute myocardial infarction (AMI) research relies increasingly on small animal models and noninvasive imaging methods such as MRI, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). However, a direct comparison among these techniques for characterization of perfusion, viability, and infarct size is lacking. Rats were studied within 18-24 hr post AMI by MRI (4.7 T) and subsequently (40-48 hr post AMI) by SPECT ((99)Tc-MIBI) and micro-PET ((18)FDG). A necrosis-specific MRI contrast agent was used to detect AMI, and a fast low angle shot (FLASH) sequence was used to acquire late enhancement and functional images contemporaneously. Infarcted regions showed late enhancement, whereas corresponding radionuclide images had reduced tracer uptake. MRI most accurately depicted AMI, showing the closest correlation and agreement with triphenyl tetrazolium chloride (TTC), followed by SPECT and PET. In some animals a mismatch of reduced uptake in normal myocardium and relatively increased (18)FDG uptake in the infarct border zone precluded conventional quantitative analysis. We performed the first quantitative comparison of MRI, PET, and SPECT for reperfused AMI imaging in a small animal model. MRI was superior to the other modalities, due to its greater spatial resolution and ability to detect necrotic myocardium directly. The observed (18)FDG mismatch likely represents variable metabolic conditions between stunned myocardium in the infarct border zone and normal myocardium and supports the use of a standardized glucose load or glucose clamp technique for PET imaging of reperfused AMI in small animals.

Simplified quantification of small animal [18F]FDG PET studies using a standard arterial input function.

PURPOSE: Arterial input function (AIF) measurement for quantification of small animal PET studies is technically challenging and limited by the small blood volume of small laboratory animals. The present study investigated the use of a standard arterial input function (SAIF) to simplify the experimental procedure. METHODS: Twelve [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET studies accompanied by serial arterial blood sampling were acquired in seven male Sprague-Dawley rats under isoflurane anaesthesia without (every rat) and with additional (five rats) vibrissae stimulation. A leave-one-out procedure was employed to validate the use of a SAIF with individual scaling by one (1S) or two (2S) arterial blood samples. RESULTS: Automatic slow bolus infusion of [(18)F]FDG resulted in highly similar AIF in all rats. The average differences of the area under the curve of the measured AIF and the individually scaled SAIF were 0.11+/-4.26% and 0.04+/-2.61% for the 1S (6-min sample) and the 2S (4-min/43-min samples) approach, respectively. The average differences between the cerebral metabolic rates of glucose (CMR(glc)) calculated using the measured AIF and the scaled SAIF were 1.31+/-5.45% and 1.30+/-3.84% for the 1S and the 2S approach, respectively. CONCLUSION: The use of a SAIF scaled by one or (preferably) two arterial blood samples can serve as a valid substitute for individual AIF measurements to quantify [(18)F]FDG PET studies in rats. The SAIF approach minimises the loss of blood and should be ideally suited for longitudinal quantitative small animal [(18)F]FDG PET studies.

In vivo detection of stem cells grafted in infarcted rat myocardium.

UNLABELLED: The evaluation of stem cell-mediated cardiomyoplasty by noninvasive in vivo imaging is critical for its clinical application. We hypothesized that dual-tracer small-animal SPECT would allow simultaneous imaging of (99m)Tc-sestamibi to assess myocardial perfusion and of (111)In-labeled stem cells to delineate stem cell engraftment. METHODS: Three to 4 million rat embryonic cardiomyoblasts (H9c2 cells) were labeled with 11.1-14.8 MBq (0.3-0.4 mCi) of (111)In-oxyquinoline and then injected into the border zones of infarcted myocardium of rats. (111)In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h after the stem cells were injected into the infarcted myocardium. To visualize the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of (99m)Tc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope pinhole SPECT was used to image (99m)Tc-sestamibi uptake simultaneously with (111)In to delineate retention of (111)In-labeled stem cells. The presence of labeled stem cells was confirmed by autoradiography and histology. RESULTS: SPECT of (99m)Tc-sestamibi was used to delineate perfusion deficits and infarcted myocardium. Bull's-eye plots indicated that the (111)In signal from the labeled stem cells overlapped the perfusion deficits identified from the (99m)Tc-sestamibi images. The (111)In signal associated with the radiolabeled stem cells could be detected with SPECT of the heart for 96 h after engraftment. CONCLUSION: This study demonstrated the feasibility of using dual-isotope pinhole SPECT for high-resolution detection of perfusion deficits with (99m)Tc-sestamibi and with (111)In-labeled stem cells grafted into the region of the infarct.