Philipp Ritt

Absolute quantification in SPECT

Single-photon emission computed tomography (SPECT) allows the three-dimensional visualization of radioactivity within the human body and is widely used for clinical purposes. In SPECT, image quality is compromised by several factors including photon attenuation, photon scatter, the partial volume effect, and motion artefacts. These variables also confound the capacity of SPECT to quantify the concentration of radioactivity within given volumes of interest in absolute units, e.g. as kilobecquerels per cubic centimetre. In the last decade, considerable technical progress has been achieved in SPECT image reconstruction, involving, in particular, the development of iterative image reconstruction techniques. Furthermore, hybrid cameras integrating a SPECT camera with an X-ray CT scanner have become commercially available. These systems allow the acquisition of SPECT and CT datasets registered to each other with a high anatomical accuracy. First studies have shown that iterative SPECT image reconstruction techniques incorporating information from SPECT/CT image datasets greatly increase the accuracy of SPECT in quantifying radioactivity concentrations in phantoms and also in humans. This new potential of SPECT may improve not only diagnostic accuracy, but also dosimetry for internal radiotherapy.

Systematic Evaluation of Phantom Fluids for Simultaneous PET/MR Hybrid Imaging

With the recent advent of integrated PET/MR hybrid systems, the need for simultaneous PET and MR phantom measurements arises. Phantom fluids that are used in stand-alone MR systems, especially in larger phantoms and at a high magnetic field strength, are not necessarily applicable in PET imaging and vice versa. In this study, different approaches to fluid selection were considered and systematically evaluated with respect to their usability for simultaneous PET/MR phantom imaging. Methods: Demineralized water, water with increased electrical conductivity, a water-oil emulsion, and monoethylene and triethylene glycol were investigated in MR and PET measurements using the most common PET tracer 18F-FDG. As an alternative to 18F-FDG, a modified PET tracer (18F-fluoride Kryptofix 222 complex) was investigated toward its ability to dissolve in pure oil, which provides good signal homogeneity in MR imaging. Measurements were performed on a 3.0 T integrated PET/MR whole-body system using a National Electrical Manufacturers Association quality-standard phantom. Results: All tested fluids dissolved the radiotracer 18F-FDG homogeneously. Regarding their suitability for MR at 3.0 T, all fluids significantly improved the homogeneity compared to pure water (increase of excitation flip angle within the tested phantom by a factor of 2.0). When the use of 18F-FDG was preferred, triethylene glycol provided the best compromise (flip angle increase by a factor of 1.13). The potential alternative tracer, 18F-fluoride Kryptofix 222 complex, dissolved in pure oil; however, it is not optimal in its tested composition because it accumulates at the bottom of the phantom during the time of measurement. Conclusion: This study provides a systematic approach toward phantom fluid selection for imaging a given quality-standard body phantom—and phantoms of comparable size—at 3.0 T. For simultaneous PET/MR scans using the standard tracer 18F-FDG, an alternative fluid to water and oil is proposed that serves as a viable option for both imaging modalities. Nevertheless, when water is preferred, ways to improve MR image homogeneity are presented. The tested alternative PET tracer enables the use of pure oil in combined scans, but the tracer composition needs to be optimized for phantom measurement applications.

Ictal SPECT in patients with rapid eye movement sleep behaviour disorder

Rapid eye movement sleep behaviour disorder is a rapid eye movement parasomnia clinically characterized by acting out dreams due to disinhibition of muscle tone in rapid eye movement sleep. Up to 80-90% of the patients with rapid eye movement sleep behaviour disorder develop neurodegenerative disorders within 10-15 years after symptom onset. The disorder is reported in 45-60% of all narcoleptic patients. Whether rapid eye movement sleep behaviour disorder is also a predictor for neurodegeneration in narcolepsy is not known. Although the pathophysiology causing the disinhibition of muscle tone in rapid eye movement sleep behaviour disorder has been studied extensively in animals, little is known about the mechanisms in humans. Most of the human data are from imaging or post-mortem studies. Recent studies show altered functional connectivity between substantia nigra and striatum in patients with rapid eye movement sleep behaviour disorder. We were interested to study which regions are activated in rapid eye movement sleep behaviour disorder during actual episodes by performing ictal single photon emission tomography. We studied one patient with idiopathic rapid eye movement sleep behaviour disorder, one with Parkinsons disease and rapid eye movement sleep behaviour disorder, and two patients with narcolepsy and rapid eye movement sleep behaviour disorder. All patients underwent extended video polysomnography. The tracer was injected after at least 10 s of consecutive rapid eye movement sleep and 10 s of disinhibited muscle tone accompanied by movements registered by an experienced sleep technician. Ictal single photon emission tomography displayed the same activation in the bilateral premotor areas, the interhemispheric cleft, the periaqueductal area, the dorsal and ventral pons and the anterior lobe of the cerebellum in all patients. Our study shows that in patients with Parkinsons disease and rapid eye movement sleep behaviour disorder-in contrast to wakefulness-the neural activity generating movement during episodes of rapid eye movement sleep behaviour disorder bypasses the basal ganglia, a mechanism that is shared by patients with idiopathic rapid eye movement sleep behaviour disorder and narcolepsy patients with rapid eye movement sleep behaviour disorder.

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.

SPECT/CT in patients with lower back pain after lumbar fusion surgery.

ObjectiveThe aim of the study was to investigate the incremental diagnostic value of skeletal hybrid imaging with single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) over conventional nuclear medical imaging in patients with lower back pain after lumbar fusion surgery (LFS). Patients and methodsThis retrospective study comprised 37 patients suffering from lower back pain after LFS in whom three-phase planar bone scintigraphies of the lumbar spine including SPECT/CT of that region had been performed. The findings visible on these imaging data sets were classified into the following five diagnostic categories: (a) metal loosening; (b) insufficient stabilizing function of the metal implants indicated by metabolically active facet joint arthritis and/or intervertebral osteochondrosis in the instrumented region; (c) adjacent instability defined as metabolically active degenerative disease in the segments adjacent to the instrumented region; (d) indeterminate; and (e) normal. ResultsIn the case of eight patients no lesions were visible on their planar scintigraphy and SPECT (planar/SPECT) or SPECT/CT images. In the remaining 29 patients, planar/SPECT disclosed 62 pathological foci of uptake within the graft region and SPECT/CT revealed 55. The rate of reclassification by SPECT/CT compared with planar/SPECT was 5/12 for lesions categorized as metal loosening by planar/SPECT, 16/29 for foci with a planar/SPECT diagnosis of insufficient stabilizing function, 7/20 when the planar/SPECT diagnosis had been adjacent instability, and 1/1 for the lesions indeterminate on planar/SPECT. Two lesions had been detected on SPECT/CT only. The overall rate of reclassification was 45.2% (28/62) (95% confidence interval, 33.4–57.5%). ConclusionBecause of its significantly higher accuracy compared with planar/SPECT, SPECT/CT should be the conventional nuclear medical procedure of choice for patients with lower back pain after LFS.

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.

Quantitative SPECT/CT.

Conventional nuclear medical imaging uses radiopharmaceuticals labeled by single-photon emitters such as Tc-99m, I-123, or I-131 in vivo. Classical clinical examples are the study of bone metabolism by bone scintigraphy with the Tc-99m-labeled polyphosphonates or of iodine transport into the thyroid gland using Tc-99m-pertechnetate. With single-photon emission-computed tomography (SPECT), the distribution of these radiopharmaceuticals within the human body is three-dimensionally visualized. Contrary to positron emission tomography (PET), current SPECT technology does not allow the quantification of regional values of radioactivity tissue concentration as SPECT images are grossly compromised by artifacts caused by photon scatter and attenuation. With the advent of hybrid imaging systems combining a SPECT camera with an X-ray computerized (CT) scanner in one gantry, reliable corrections for these artifacts seem possible, allowing truly quantitative SPECT.

Impact of Point-Spread Function Modeling on PET Image Quality in Integrated PET/MR Hybrid Imaging

The aim of this study was to systematically assess the quantitative and qualitative impact of including point-spread function (PSF) modeling into the process of iterative PET image reconstruction in integrated PET/MR imaging. Methods: All measurements were performed on an integrated whole-body PET/MR system. Three substudies were performed: an 18F-filled Jaszczak phantom was measured, and the impact of including PSF modeling in ordinary Poisson ordered-subset expectation maximization reconstruction on quantitative accuracy and image noise was evaluated for a range of radial phantom positions, iteration numbers, and postreconstruction smoothing settings; 5 representative datasets from a patient population (total n = 20, all oncologic 18F-FDG PET/MR) were selected, and the impact of PSF on lesion activity concentration and image noise for various iteration numbers and postsmoothing settings was evaluated; and for all 20 patients, the influence of PSF modeling was investigated on visual image quality and number of detected lesions, both assessed by clinical experts. Additionally, the influence on objective metrics such as changes in SUVmean, SUVpeak, SUVmax, and lesion volume was assessed using the manufacturer-recommended reconstruction settings. Results: In the phantom study, PSF modeling significantly improved activity recovery and reduced the image noise at all radial positions. This effect was measurable only at a high number of iterations (>10 iterations, 21 subsets). In the patient study, again, PSF increased the detected activity in the patient’s lesions at concurrently reduced image noise. Contrary to the phantom results, the effect was notable already at a lower number of iterations (>1 iteration, 21 subsets). Lastly, for all 20 patients, when PSF and no-PSF reconstructions were compared, an identical number of congruent lesions was found. The overall image quality of the PSF reconstructions was rated better when compared with no-PSF data. The SUVs of the detected lesions with PSF were substantially increased in the range of 6%–75%, 5%–131%, and 5%–148% for SUVmean, SUVpeak, and SUVmax, respectively. A regression analysis showed that the relative increase in SUVmean/peak/max decreases with increasing lesion size, whereas it increases with the distance from the center of the PET field of view. Conclusion: In whole-body PET/MR hybrid imaging, PSF-based PET reconstructions can improve activity recovery and image noise, especially at lateral positions of the PET field of view. This has been demonstrated quantitatively in phantom experiments as well as in patient imaging, for which additionally an improvement of image quality could be observed.

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.

GATE Monte Carlo simulations for variations of an integrated PET/MR hybrid imaging system based on the Biograph mMR model.

A simulation toolkit, GATE (Geant4 Application for Tomographic Emission), was used to develop an accurate Monte Carlo (MC) simulation of a fully integrated 3T PET/MR hybrid imaging system (Siemens Biograph mMR). The PET/MR components of the Biograph mMR were simulated in order to allow a detailed study of variations of the system design on the PET performance, which are not easy to access and measure on a real PET/MR system. The 3T static magnetic field of the MR system was taken into account in all Monte Carlo simulations. The validation of the MC model was carried out against actual measurements performed on the PET/MR system by following the NEMA (National Electrical Manufacturers Association) NU 2-2007 standard. The comparison of simulated and experimental performance measurements included spatial resolution, sensitivity, scatter fraction, and count rate capability. The validated system model was then used for two different applications. The first application focused on investigating the effect of an extension of the PET field-of-view on the PET performance of the PET/MR system. The second application deals with simulating a modified system timing resolution and coincidence time window of the PET detector electronics in order to simulate time-of-flight (TOF) PET detection. A dedicated phantom was modeled to investigate the impact of TOF on overall PET image quality. Simulation results showed that the overall divergence between simulated and measured data was found to be less than 10%. Varying the detector geometry showed that the system sensitivity and noise equivalent count rate of the PET/MR system increased progressively with an increasing number of axial detector block rings, as to be expected. TOF-based PET reconstructions of the modeled phantom showed an improvement in signal-to-noise ratio and image contrast to the conventional non-TOF PET reconstructions. In conclusion, the validated MC simulation model of an integrated PET/MR system with an overall accuracy error of less than 10% can now be used for further MC simulation applications such as development of hardware components as well as for testing of new PET/MR software algorithms, such as assessment of point-spread function-based reconstruction algorithms.