Kathy Willowson

An Evidence-Based Review of Quantitative SPECT Imaging and Potential Clinical Applications

SPECT has traditionally been regarded as nonquantitative. Advances in multimodality γ-cameras (SPECT/CT), algorithms for image reconstruction, and sophisticated compensation techniques to correct for photon attenuation and scattering have, however, now made quantitative SPECT viable in a manner similar to quantitative PET (i.e., kBq⋅cm−3, standardized uptake value). This review examines the evidence for quantitative SPECT and demonstrates clinical studies in which the accuracy of the reconstructed SPECT data has been assessed in vivo. SPECT reconstructions using CT-based compensation corrections readily achieve accuracy for 99mTc to within ±10% of the known concentration of the radiotracer in vivo. Quantification with other radionuclides is also being introduced. SPECT continues to suffer from poorer photon detection efficiency (sensitivity) and spatial resolution than PET; however, it has the benefit in some situations of longer radionuclide half-lives, which may better suit the biologic process under examination, as well as the ability to perform multitracer studies using pulse height spectroscopy to separate different radiolabels.

Quantitative SPECT reconstruction using CT-derived corrections

A method for achieving quantitative single-photon emission computed tomography (SPECT) based upon corrections derived from x-ray computed tomography (CT) data is presented. A CT-derived attenuation map is used to perform transmission-dependent scatter correction (TDSC) in conjunction with non-uniform attenuation correction. The original CT data are also utilized to correct for partial volume effects in small volumes of interest. The accuracy of the quantitative technique has been evaluated with phantom experiments and clinical lung ventilation/perfusion SPECT/CT studies. A comparison of calculated values with the known total activities and concentrations in a mixed-material cylindrical phantom, and in liver and cardiac inserts within an anthropomorphic torso phantom, produced accurate results. The total activity in corrected ventilation-subtracted perfusion images was compared to the calibrated injected dose of [(99m)Tc]-MAA (macro-aggregated albumin). The average difference over 12 studies between the known and calculated activities was found to be -1%, with a range of +/-7%.

Quantitative SPECT/CT: SPECT joins PET as a quantitative imaging modality

The introduction of combined modality single photon emission computed tomography (SPECT)/CT cameras has revived interest in quantitative SPECT. Schemes to mitigate the deleterious effects of photon attenuation and scattering in SPECT imaging have been developed over the last 30 years but have been held back by lack of ready access to data concerning the density of the body and photon transport, which we see as key to producing quantitative data. With X-ray CT data now routinely available, validations of techniques to produce quantitative SPECT reconstructions have been undertaken. While still suffering from inferior spatial resolution and sensitivity compared to positron emission tomography (PET) imaging, SPECT scans nevertheless can be produced that are as quantitative as PET scans. Routine corrections are applied for photon attenuation and scattering, resolution recovery, instrumental dead time, radioactive decay and cross-calibration to produce SPECT images in units of kBq.ml−1. Though clinical applications of quantitative SPECT imaging are lacking due to the previous non-availability of accurately calibrated SPECT reconstructions, these are beginning to emerge as the community and industry focus on producing SPECT/CT systems that are intrinsically quantitative.

Investigation of the relationship between linear attenuation coefficients and CT Hounsfield units using radionuclides for SPECT

This study has investigated the relationship between linear attenuation coefficients (mu) and Hounsfield units (HUs) for six materials covering the range of values found clinically. Narrow-beam mu values were measured by performing radionuclide transmission scans using (99m)Tc, (123)I, (131)I, (201)Tl and (111)In. The mu values were compared to published data. The relationships between mu and HU were determined. These relationships can be used to convert computed tomography (CT) images to mu-maps for single photon emission computed tomography (SPECT) attenuation correction.

SPECT/CT in V/Q scanning.

Combining the functional data provided by single-photon emission computed tomography (SPECT) with the anatomical information provided by CT has been shown to improve overall diagnostic accuracy in many areas of nuclear medicine. Although planar lung scans have often relied on correlation with a chest x-ray to help optimize scan interpretation, the advent of 3D lung imaging with SPECT provides the opportunity to combine lung perfusion data with CT images. This can be done by performing the study on a hybrid SPECT/CT scanner, with the CT acquisition typically performed with the use of low-dose parameters, rather than full diagnostic quality settings, or by software fusion with a fully diagnostic CT or a contrast-enhanced CT pulmonary angiogram. Such an approach has been shown to improve specificity and overall accuracy of ventilation/perfusion scintigraphy as well as facilitating more accurate clot localization. With the increased availability of hybrid SPECT/CT scanners, such an approach can be implemented in most imaging departments with little additional acquisition time or radiation dose. Misregistration caused by respiratory motion can impact combined studies, although this can be minimized with attention to patient breathing patterns during image acquisition. For patients with lung cancer, ventilation/perfusion SPECT/CT may have a role in allowing the optimal selection of radiotherapy fields and can improve the preoperative quantification of lung function before resection.

Quantitative 90Y image reconstruction in PET

PURPOSE Positron emission tomography (PET) imaging is increasingly used to confirm localization of (90)Y microspheres in the treatment of liver cancer. The aim of this work was to evaluate the quantification of (90)Y PET data on a current generation time-of-flight extended axial field-of-view PET∕CT camera. METHODS The International Electrotechnical Commission (IEC) body phantom was used to image six spheres of varying diameters containing a high concentration of (90)Y solution in a lower concentration background. Multiple PET studies were acquired of the phantom over a number of days during decay. The effect of reconstruction parameters in OSEM was evaluated both qualitatively and quantitatively. Expected values of total phantom activity, hot-sphere, and background concentration were compared to measured values from the reconstructed data as well as misplaced events in a cold insert. The partial volume effect was measured and the effects of time-of-flight during reconstruction on hot contrast recovery and background variability were evaluated according to NEMA-NU2-2007 protocol, and compared to that for (18)F. The method was applied to a patient study following radioembolization to estimate actual implanted radioactivity. RESULTS Increasing the number of OSEM iterations visually deteriorated image data and resulted in a larger overall difference of hot concentration measures when considering both count high and count poor data. The average difference between measured and true total activity and background concentration was found to be +5% and +5%, respectively. Measured hot-sphere concentration was linear across all datasets, and while estimated to be within error of expected values, was consistently underestimated by an average of 23%, 12%, and 8%, when using a CT-derived, 50% threshold-derived, and 70% threshold-derived volume of interest, respectively. Partial volume effects were evident in all but the largest sphere, following an expected relationship between object size and recovery coefficient, inferior to that of (18)F. Time-of-flight improved contrast of hot-spheres but resulted in a deterioration of background variability, following a similar trend to that seen with (18)F. The patient data estimated a total implanted activity of 1643 MBq, compared to the intended dose of 1780 MBq, with a difference most likely due to residual and error in the initial dose calibration. CONCLUSIONS Quantitative (90)Y PET with a state-of-the-art PET∕CT scanner with time-of-flight and standard corrections for photon interactions demonstrates consistent and acceptable measures of total activity and radionuclide concentration across a range of realistic count statistics. The method is suitable for measuring the radioactivity delivered at the time of (90)Y therapy with the potential for absorbed dose calculation.

Quantitative and qualitative assessment of Yttrium-90 PET/CT imaging.

Yttrium-90 is known to have a low positron emission decay of 32 ppm that may allow for personalized dosimetry of liver cancer therapy with 90Y labeled microspheres. The aim of this work was to image and quantify 90Y so that accurate predictions of the absorbed dose can be made. The measurements were performed within the QUEST study (University of Sydney, and Sirtex Medical, Australia). A NEMA IEC body phantom containing 6 fillable spheres (10–37 mm ∅) was used to measure the 90Y distribution with a Biograph mCT PET/CT (Siemens, Erlangen, Germany) with time-of-flight (TOF) acquisition. A sphere to background ratio of 8∶1, with a total 90Y activity of 3 GBq was used. Measurements were performed for one week (0, 3, 5 and 7 d). he acquisition protocol consisted of 30 min-2 bed positions and 120 min-single bed position. mages were reconstructed with 3D ordered subset expectation maximization (OSEM) and point spread function (PSF) for iteration numbers of 1–12 with 21 (TOF) and 24 (non-TOF) subsets and CT based attenuation and scatter correction. Convergence of algorithms and activity recovery was assessed based on regions-of-interest (ROI) analysis of the background (100 voxels), spheres (4 voxels) and the central low density insert (25 voxels). For the largest sphere, the recovery coefficient (RC) values for the 30 min –2-bed position, 30 min-single bed and 120 min-single bed were 1.12±0.20, 1.14±0.13, 0.97±0.07 respectively. For the smaller diameter spheres, the PSF algorithm with TOF and single bed acquisition provided a comparatively better activity recovery. Quantification of Y-90 using Biograph mCT PET/CT is possible with a reasonable accuracy, the limitations being the size of the lesion and the activity concentration present. At this stage, based on our study, it seems advantageous to use different protocols depending on the size of the lesion.

Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy

Prostate‐specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high‐binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides. Early clinical studies evaluating the safety and efficacy of Lu PSMA therapy have demonstrated promising results with a significant proportion of men with metastatic prostate cancer, who have already failed other therapies, responding clinically to Lu PSMA. This review discusses the practical issues of administering Lu PSMA, and gives an overview of the findings from currently published trials in regards to treatment response rates, expected toxicities and safety.

90Y -PET imaging: Exploring limitations and accuracy under conditions of low counts and high random fraction

PURPOSE (90)Y -positron emission tomography (PET) imaging is becoming a recognized modality for postinfusion quantitative assessment following radioembolization therapy. However, the extremely low counts and high random fraction associated with (90)Y -PET may significantly impair both qualitative and quantitative results. The aim of this work was to study image quality and noise level in relation to the quantification and bias performance of two types of Siemens PET scanners when imaging (90)Y and to compare experimental results with clinical data from two types of commercially available (90)Y microspheres. METHODS Data were acquired on both Siemens Biograph TruePoint [non-time-of-flight (TOF)] and Biograph microcomputed tomography (mCT) (TOF) PET/CT scanners. The study was conducted in three phases. The first aimed to assess quantification and bias for different reconstruction methods according to random fraction and number of true counts in the scan. The NEMA 1994 PET phantom was filled with water with one cylindrical insert left empty (air) and the other filled with a solution of (90)Y . The phantom was scanned for 60 min in the PET/CT scanner every one or two days. The second phase used the NEMA 2001 PET phantom to derive noise and image quality metrics. The spheres and the background were filled with a (90)Y solution in an 8:1 contrast ratio and four 30 min acquisitions were performed over a one week period. Finally, 32 patient data (8 treated with Therasphere(®) and 24 with SIR-Spheres(®)) were retrospectively reconstructed and activity in the whole field of view and the liver was compared to theoretical injected activity. RESULTS The contribution of both bremsstrahlung and LSO trues was found to be negligible, allowing data to be decay corrected to obtain correct quantification. In general, the recovered activity for all reconstruction methods was stable over the range studied, with a small bias appearing at extremely high random fraction and low counts for iterative algorithms. Point spread function (PSF) correction and TOF reconstruction in general reduce background variability and noise and increase recovered concentration. Results for patient data indicated a good correlation between the expected and PET reconstructed activities. A linear relationship between the expected and the measured activities in the organ of interest was observed for all reconstruction method used: a linearity coefficient of 0.89 ± 0.05 for the Biograph mCT and 0.81 ± 0.05 for the Biograph TruePoint. CONCLUSIONS Due to the low counts and high random fraction, accurate image quantification of (90)Y during selective internal radionuclide therapy is affected by random coincidence estimation, scatter correction, and any positivity constraint of the algorithm. Nevertheless, phantom and patient studies showed that the impact of number of true and random coincidences on quantitative results was found to be limited as long as ordinary Poisson ordered subsets expectation maximization reconstruction algorithms with random smoothing are used. Adding PSF correction and TOF information to the reconstruction greatly improves the image quality in terms of bias, variability, noise reduction, and detectability. On the patient studies, the total activity in the field of view is in general accurately measured by Biograph mCT and slightly overestimated by the Biograph TruePoint.

In vivo validation of quantitative SPECT in the heart

Background: We have previously developed and validated a method to achieve quantitative SPECT data based on CT‐derived corrections, for the radionuclide 99mTc in phantoms and in man for lung scanning. This clinical study was performed to investigate the accuracy of this method when applied to cardiac blood pool imaging. The study involves tagging the radionuclide 99mTc to erythrocytes in a sample of the subject’s blood before it is re‐injected. After a short time, the radiolabelled cells achieve an equilibrium concentration in the blood pool, such that SPECT imaging allows the radioactivity concentration of blood present in the left ventricle to be measured. Methods and results: Absolute concentration of radioactivity inside the left ventricle of the heart was compared to true concentrations measured directly from a peripheral venous blood sample taken from the subject at the time of scanning. In 12 subjects, the average difference between the measured and true concentrations was found to be within ∼1% of the true value with a range of (−6 to +5)%. Conclusions: This study demonstrates the accuracy of CT‐based quantitative SPECT in clinical cardiac blood pool imaging, and we anticipate that similar accuracy could be achieved in the myocardium.