James C. Sanders

Quantitative SPECT/CT Imaging of (177)Lu with In Vivo Validation in Patients Undergoing Peptide Receptor Radionuclide Therapy.

PurposeThe purpose of this study is to extend an established SPECT/CT quantitation protocol to 177Lu and validate it in vivo using urine samples, thus providing a basis for 3D dosimetry of 177Lu radiotherapy and improvement over current planar methods which improperly account for anatomical variations, attenuation, and overlapping organs.ProceduresIn our quantitation protocol, counts in images reconstructed using an ordered subset-expectation maximization algorithm are converted to kilobecquerels per milliliter using a calibration factor derived from a phantom experiment. While varying reconstruction parameters, we tracked the ratio of image to true activity concentration (recovery coefficient, RC) in hot spheres and a noise measure in a homogeneous region. The optimal parameter set was selected as the point where recovery in the largest three spheres (16, 8, and 4 ml) stagnated, while the noise continued to increase.Urine samples were collected following 12 SPECT/CT acquisitions of patients undergoing [177Lu]DOTATATE therapy, and activity concentrations were measured in a well counter. Data was reconstructed using parameters chosen in the phantom experiment, and estimated activity concentration from the images was compared to the urine values to derive RCs.ResultsIn phantom data, our chosen parameter set yielded RCs in 16, 8, and 4 ml spheres of 80.0, 74.1, and 64.5 %, respectively. For patients, the mean bladder RC was 96.1 ± 13.2 % (range, 80.6–122.4 %), with a 95 % confidence interval between 88.6 and 103.6 %. The mean error of SPECT/CT concentrations was 10.1 ± 8.3 % (range, −19.4–22.4 %).ConclusionsOur results show that quantitative 177Lu SPECT/CT in vivo is feasible but could benefit from improved reconstruction methods. Quantifying bladder activity is analogous to determining the amount of activity in the kidneys, an important task in dosimetry, and our results provide a useful benchmark for future efforts.

First Experience With SPECT/CT Using a 99mTc-Labeled Inhibitor for Prostate-Specific Membrane Antigen in Patients With Biochemical Recurrence of Prostate Cancer.

Aim Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate cancers (PCs). Here, we report our first experience using the 99mTc-labeled PSMA inhibitor MIP-1404 (Progenics Pharmaceuticals, Inc, Tarrytown, NY) in 60 patients with biochemically recurrent PC. Methods Whole-body planar scintigraphy and SPECT/CT of the lower abdominal pelvic region of 60 patients with biochemical relapse of PC were analyzed retrospectively. In these subjects, an average dose of 733.1 ± 49.5 MBq (19.8 ± 1.3 mCi) 99mTc-labeled MIP-1404 was injected 4 to 5 hours prior to imaging. In addition to visual evaluation, SUVmax were determined in the tumor lesions using a previously developed protocol for quantitative SPECT/CT. Results In 42 of 60 patients, 99mTc–MIP-1404–positive lesions could be detected (70%; 95% confidence interval [CI], 0.58-0.82). Twenty patients had 99mTc–MIP-1404–positive lymph nodes suggestive of metastasis, 14 patients had pathological uptake in the prostate region indicative of local recurrence, and for another 19 patients, there was tracer accumulation in the skeleton (n = 18) or lungs (n = 1). Detection rate was 91.4% (95% CI, 0.82-1) at prostate-specific antigen levels greater than 2 ng/mL and 40.0% (95% CI, 0.21-0.59) at lower prostate-specific antigen values (P < 0.01). Of the 60 patients, in total, 82 positive lesions were analyzed quantitatively. Average SUVmax of the lesions was 16.3 ± 21.6 with a range of 1.7 to 142.9. Conclusion 99mTc-labeled PSMA inhibitor MIP-1404 is a promising SPECT tracer for detection of locally recurrent or metastatic prostate cancer.

Fully Automated Data-Driven Respiratory Signal Extraction From SPECT Images Using Laplacian Eigenmaps

We propose a data-driven method for extracting a respiratory surrogate signal from SPECT list-mode data. The approach is based on dimensionality reduction with Laplacian Eigenmaps. By setting a scale parameter adaptively and adding a series of post-processing steps to correct polarity and normalization between projections, we enable fully-automatic operation and deliver a respiratory surrogate signal for the entire SPECT acquisition. We validated the method using 67 patient scans from three acquisition types (myocardial perfusion, liver shunt diagnostic, lung inhalation/perfusion) and an Anzai pressure belt as a gold standard. The proposed method achieved a mean correlation against the Anzai of 0.81 ± 0.17 (median 0.89). In a subsequent analysis, we characterize the performance of the method with respect to count rates and describe a predictor for identifying scans with insufficient statistics. To the best of our knowledge, this is the first large validation of a data-driven respiratory signal extraction method published thus far for SPECT, and our results compare well with those reported in the literature for such techniques applied to other modalities such as MR and PET.

Data-driven respiratory signal extraction for SPECT imaging using Laplacian Eigenmaps

In Single Photon Emission-Computed Tomography (SPECT) imaging, respiratory motion may lead to artifacts and loss of quantitative accuracy. To compensate for this motion, a respiratory surrogate signal representing the patients respiratory state over time is required. In practice, this surrogate signal is obtained via sensor-based approaches, but we seek to develop a data-driven solution that requires no external hardware. In this work, we compare two such methods, one linear and one non-linear, based on dimensionality reduction: Principle Component Analysis (PCA) and Laplacian Eigenmaps (LE). Our aim is to apply both to conventional SPECT and assess the feasibility of data-driven respiratory surrogate signal extraction for this modality. We expect that LE, which is less sensitive to outliers in data, will outperform PCA at high levels of image noise. Two phantom acquisitions were performed: one in which a sphere in cold background was translated axially by a piston actuator (dynamic), and a warm background with no sphere (static). Using binomial subsampling, both datasets were combined at various Signal-to-Noise Ratios (SNRs). LE and PCA surrogate signals were computed and compared via Pearsons correlation to the truth signal obtained from the actuator. As a follow-up, LE and PCA estimates from 27 cardiac SPECT acquisitions were compared to a simultaneously acquired signal from a pressure sensor embedded in an elastic belt. In the phantom experiment, correlations between LE/PCA and truth were >0.9 for all SNR>5. For SNR<;5, PCA deteriorated rapidly, whereas LE remained stable through SNR=2.5. For the patient validation, LE and PCA yielded average correlations of 0.86±0.14 and 0.37±0.26, respectively. The phantom experiment indicated that LE outperforms PCA for low-SNR data. This conclusion was supported by the superior performance of LE for patient datasets, where noise may be high. However, the present work is limited by the simplistic motion present in the phantom experiment and the limited scope of the patient validation.

99mTc-MIP-1404-SPECT/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer

99mTc‐MIP‐1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT‐compatible 99mTc‐labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse.

Absolute SPECT/CT quantification of cerebral uptake of 99mTc-HMPAO for patients with neurocognitive disorders.

UNLABELLED It was reported from planar imaging studies that the cerebral uptake of injected 99mTc-HMPAO activity is about 4-7% in humans. Recent work has shown that modern SPECT/CT devices are able to quantify the tissue concentration of radioactivity in vivo in absolute units (Bq/ml), while avoiding the limitations of planar techniques. The aims of this study were (a) to determine the cerebral uptake of 99mTc-HMPAO in absolute units in SPECT/CT, (b) to investigate potential differences in absolute tracer uptake for patients suspected of dementia. PATIENTS, METHODS We performed 99mTc-HMPAO SPECT/CT in 65 patients with suspected dementia. 99mTc-HMPAO uptake was determined using a previously published quantitative SPECT/CT protocol. The absolute HMPAO uptake and the results of a regionalized analysis were compared for MMSE and NINCDS-ADRDA based patient groups. RESULTS The mean absolute uptake of 99mTc-HMPAO for our patient population was 4.3 ± 0.8% of the injected dose. The uptake, as well as the regionalized analysis yielded significantly different results for low (≤23) and high (>23) MMSE groups and also for some of the NINCDS-ADRDA groups. CONCLUSION Our results show that the absolute cerebral uptake of 99mTc-HMPAO is in the range of previously reported results, obtained by planar techniques. Absolute uptake is significantly different between the patient groups.

Investigation of Single Photon Emission Computed Tomography Acquired on Helical Trajectories

This study compares the quality of single photon emission computed tomography images obtained using step-and-shoot and helical trajectories. Monte Carlo simulations of an extended phantom on both trajectories were performed using a parallel hole collimator. Standard filtered-backprojection was used for reconstruction. Both trajectories collected data for the same amount of time. Corresponding to equivalent useful acquisition times, the background signal-to-noise ratios and sphere to background contrasts were roughly equivalent in both reconstructions. However, the helical trajectory requires 20% less true acquisition time due to the elimination of delay due to detector repositioning. Helical trajectories in SPECT can thus reduce overall acquisition time while having negligible effects on image quality.