SPET Imaging Research Articles

Protection of dopaminergic nigrostriatal afferents by GDNF delivered by microspheres in a rodent model of Parkinson's disease.

The use of glial cell line-derived neurotrophic factor (GDNF) appears to be a promising strategy to promote survival and function of the nigrostriatal dopaminergic pathway damaged in Parkinson's disease (PD). However, effective intracerebral administration is required for optimal therapeutic benefit and tools to evaluate such therapies must be developed. A rodent model of PD was therefore developed using striatal injection of 6-hydroxydopamine (6-OHDA) with simultaneous implantation of GDNF-delivering microspheres. The effects of GDNF released from microspheres were assessed by classical methods such as amphetamine-induced rotating behavior and tyrosine hydroxylase (TH) immunoreactivity, as well as by quantitative autoradiography using PE2I, a dopamine transporter (DAT) radiotracer, which is also suitable for SPET imaging in humans. 6-OHDA-lesioned animals that received microspheres without GDNF were used as controls. During the first 3 weeks after simultaneous lesion and implantation, the amphetamine-induced rotating behavior of GDNF-treated rats was improved compared to controls and an increase in TH expression (+26%) was measured in the striatum 6 weeks after lesion. In accordance with these results, an increase in striatal PE2I-labeled DAT density was obtained (+17%) after 3 and 6 weeks of treatment. In conclusion, this study demonstrates the neuroprotective action of GDNF delivered by microspheres and suggests that PE2I may be an appropriate radiotracer for use in SPET scintigraphy to follow up treatment of PD in humans.

Against

The development of reliable and accurate devices for the correction of nonuniform soft tissue attenuation is essential for the future clinical use of SPET myocardial perfusion imaging. In addition to abolishing false-positive defects, which is the chief goal, such corrected SPET images may allow for improved detection of coronary artery disease and perhaps ultimately for true quantification of regional myocardial blood flow. Although progress has been made, most existing attenuation correction devices are not yet ready for prime time. To date the literature shows as many positive results as negative results. There is considerable uncertainty, confusion, and skepticism about the true reliability and value of currently available attenuation correction packages. Although commonly referred to as "attenuation correction devices," these packages are in fact much more complex systems and contain novel mechanical designs, novel image acquisition and image reconstruction algorithms, scatter correction, and depth-dependent resolution compensation, in addition to attenuation correction. Each of these variables needs to be better understood and tested prior to clinical implementation. Although the general concepts are shared, there are as may different approaches to attenuation correction as there are vendors. In order to minimize the confusion of potential buyers about such complex systems, it is desirable that, before attenuation correction is implemented in routine clinical practice, each attenuation correction device is rigorously tested using a standardized testing protocol. Potential buyers of equipment should be able to compare the results of testing with various devices against predefined criteria in order to make an educated decision. Such standards have as yet not been developed. At the present time it is unclear whether attenuation correction of cardiac SPET will remain the emperor's new clothes or will develop into a fashionable Armani suit. Until further progress has been made, one cannot recommend attenuation correction devices for routine clinical practice.

Clinical experience with 123I β-CIT SPET imaging in atypical tremor patients

Clinical experience with 123I β-CIT SPET imaging in atypical tremor patients

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers.

Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [123I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of +/-110 MBq [123I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [123I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [123I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [123I]FP-CIT binding ratios than males. This effect of gender on [123I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies.

Improvement of brain perfusion SPET using iterative reconstruction with scatter and non-uniform attenuation correction.

Filtered back-projection (FBP) is generally used as the reconstruction method for single-photon emission tomography although it produces noisy images with apparent streak artefacts. It is possible to improve the image quality by using an algorithm with iterative correction steps. The iterative reconstruction technique also has an additional benefit in that computation of attenuation correction can be included in the process. A commonly used iterative method, maximum-likelihood expectation maximisation (ML-EM), can be accelerated using ordered subsets (OS-EM). We have applied to the OS-EM algorithm a Bayesian one-step late correction method utilising median root prior (MRP). Methodological comparison was performed by means of measurements obtained with a brain perfusion phantom and using patient data. The aim of this work was to quantitate the accuracy of iterative reconstruction with scatter and non-uniform attenuation corrections and post-filtering in SPET brain perfusion imaging. SPET imaging was performed using a triple-head gamma camera with fan-beam collimators. Transmission and emission scans were acquired simultaneously. The brain phantom used was a high-resolution three-dimensional anthropomorphic JB003 phantom. Patient studies were performed in ten chronic pain syndrome patients. The images were reconstructed using conventional FBP and iterative OS-EM and MRP techniques including scatter and nonuniform attenuation corrections. Iterative reconstructions were individually post-filtered. The quantitative results obtained with the brain perfusion phantom were compared with the known actual contrast ratios. The calculated difference from the true values was largest with the FBP method; iteratively reconstructed images proved closer to the reality. Similar findings were obtained in the patient studies. The plain OS-EM method improved the contrast whereas in the case of the MRP technique the improvement in contrast was not so evident with post-filtering.

Biodistribution and dosimetry of [123I]iodo-PK 11195: a potential agent for SPET imaging of the peripheral benzodiazepine receptor.

The highest concentrations of the peripheral benzodiazepine receptor (PBR) are found in the kidneys and heart. In addition, the PBR has been reported to reflect neuro-inflammatory damage by co-localisation with activated microglia. PK 11195 is a high-affinity ligand for the PBR. The aim of this study was to investigate in humans the biodistribution and dosimetry of [123I]iodoPK 11195, a potential single-photon emission tomography tracer for the PBR. Five healthy volunteers were injected with 112 MBq of [123I]iodo-PK 11195. Sequential whole-body scans were performed up to 72 h post injection. Multiple blood samples were taken, and urine was collected to measure the fraction voided by the renal system. Decay-corrected regions of interest of the whole-body images were analysed, and geometric mean count rates were used to determine organ activity. Organ absorbed doses and effective dose were calculated using the MIRD method. [123I]iodo-PK 11195 was rapidly cleared from the blood, mainly by the hepatobiliary system. Approximately 22% was voided in urine after 48 h. Average organ residence times were 0.74, 0.44 and 0.29 h for the liver, upper large intestine and lower large intestine, respectively. The testes received the highest dose, 109.4 microGy/MBq. All other organs investigated received doses of less than 50 microGy/MBq. The effective dose was 40.3 microSv/MBq. In conclusion, [123I]iodo-PK 11195 is a suitable agent for the visualisation of the PBR and indirectly for the imaging of neuro-inflammatory lesions. Taking into account the radiation burden of 7.46 mSv following an administration of 185 MBq, a [123I]iodo-PK 11195 investigation has to be considered an ICRP risk category IIb investigation.

60. Registration of SPET and CT abdominal images using a symmetric correlation ratio

s: Abstracts of the 30th Annual Scientific Meeting of the Australian and New Zealand Society of Nuclear Medicine

Absorbed dose estimates for 131I-labelled monoclonal antibody therapy in patients with intraperitoneal pseudomyxoma.

Seven patients with intraperitoneal pseudomyxoma originating from the appendix (4 cases) and from the ovary (3 cases) were treated with radioimmunotherapy. During the therapy, nine infusions of 3.0-4.2 GBq of 131I-labelled B72.3 monoclonal antibody were administered. We developed three-dimensional dose calculation software that can utilize activity maps based on SPET images to calculate the absorbed dose distribution using point source kernels. The dose calculation program was employed to calculate absorbed doses to various organs. The calculated dose distributions enable us to evaluate the variation in dose within the organs, which is normally not available using approaches based on geometric models. The patient-specific absorbed dose calculations were compared with doses based on a model that uses photon S-factors derived from a standard phantom. The compared doses agreed well on average, but in some organs showed large discrepancies.

1. Can high-resolution SPET imaging successfuly direct treatment of low back pain?

s: Abstracts of the Twenty-Eighth Annual Meeting of The British Nuclear Medicine Society Brighton Conference Centre, 10-12 April 2000: Monday 10 April BONE East Wing-Alpha Hall

53. Devising a quality assurance schedule for brain SPET imaging with a dual-headed, variable-angle gamma

s: Abstracts of the Twenty-Eighth Annual Meeting of The British Nuclear Medicine Society Brighton Conference Centre, 10-12 April 2000: Tuesday 11 April PHYSICS 1: QUALITY ASSURANCE East Wing-Beta Hall

38. Economic evaluation of CT and SPET imaging to assess acute ischaemic stroke patients for thrombolysis

s: Abstracts of the Twenty-Eighth Annual Meeting of The British Nuclear Medicine Society Brighton Conference Centre, 10-12 April 2000: Tuesday 11 April NEUROLOGY/PSYCHIATRY East Wing-Alpha Hall

Effect of exercise induced hyperlactatemia on the biodistribution and metabolism of iodine-123-15(p-iodophenyl)-3-R,S-methyl pentadecanoic acid in normal volunteers.

We have evaluated the biodistribution and metabolism of iodine-123-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) in the presence of increased lactate levels induced by short-term heavy exercise. Five healthy male subjects received 159 MBq (+/- 13 MBq) 123I-BMIPP at rest and a week later after they performed a maximal exercise test using a bicycle ergometer. Planar and tomographic images were obtained with a dual-head gamma camera up to 4 h after administration of the tracer. Multiple blood samples were taken at different time points for blood clearance, substrate concentration measurements and for HPLC analysis of metabolites. The exercise test did not alter plasma glucose and non-esterified fatty acid concentrations, but blood lactate increased from 1.12 mmol/l at rest to 9.26 mmol/l with maximal exercise. After exercise, BMIPP showed a significantly faster plasma clearance than at rest and the production of PIPA, the end metabolite of BMIPP oxidation, was reduced. Activity in the heart was similar after exercise and at rest on planar images 15 min after injection (4.83 +/- 0.50% ID vs 4.80 +/- 0.43% ID, P = NS), although the myocardium-to-cavity activity ratio, as determined on the SPET images 20 min after tracer injection, was slightly increased after the exercise test (4.20 +/- 0.63 vs 3.78 +/- 1.34 at rest, P = NS). Significantly increased activity was observed in a leg muscle region of interest after exercise (4.98 +/- 0.50% ID vs 3.93 +/- 0.44% ID at rest, P = 0.02). Between early and late images, tracer washout from the myocardium increased from 20.72% at rest to 36.72% after exercise (P < 0.05), but was unchanged for liver and leg muscles. The metabolic and physiological alterations induced by exercise do not degrade image quality of BMIPP scintigraphy. On the contrary, exercise-induced hyperlactatemia seems to enhance myocardium-to-cavity activity ratios on SPET images, although this effect does not reach statistical significance in this small group of normal subjects. These findings further support the robustness of BMIPP SPET in varied metabolic environments.

Effect of radiochemical purity of 99Tcm-Q12 on myocardial SPET image quality.

In myocardial perfusion SPET studies with 99Tcm-Q12, we observed that some patients had high liver uptake that interfered significantly in the assessment of the inferior wall. The aim of this study was to assess the effects of the radiochemical purity of 99Tcm-Q12 on liver uptake. Thirty-one patients undergoing routine myocardial infarction perfusion studies were evaluated. The radiochemical purity of 99Tcm-Q12 was determined using HPLC. Venous blood samples taken 50 min after injection of 99Tcm-Q12 during peak exercise were also analysed. Liver uptake was expressed as the liver-to-heart ratio. In addition, the SPET images were classified by two experienced nuclear medicine specialists into three groups representing high-quality images (n = 7), images with high general background activity (n = 13) and images with high liver and/or intestinal uptake (n = 11). The liver-to-heart ratio correlated inversely with the radiochemical purity of 99Tcm-Q12 (r = -0.65, P < 0.001) and unchanged 99Tcm-Q12 in plasma (r = -0.44, P < 0.02). The radiochemical purity of 99Tcm-Q12 was significantly lower in the group with high liver uptake (60.1 +/- 4.2%) than in the group with good-quality images (81.8 +/- 5.6%, P < 0.01) or with high background activity (82.3 +/- 2.5%, P < 0.01). In conclusion, the radiochemical purity of 99Tcm-Q12 has a significant inverse correlation with the liver-to-heart ratio; thus, the high radiochemical purity of 99Tcm-Q12 should be confirmed to prevent interference by liver uptake.

MRI-SPET and SPET-SPET brain co-registration: evaluation of the performance of eight different algorithms.

The aim of this study was to assess the accuracy and computing time needed for MRI-SPET and SPET-SPET brain co-registration using eight different algorithms (Hermes software from Nuclear Diagnostics Ltd run on a SUN Ultra Sparc 2) to determine the clinically most suitable algorithm. MRI-SPET co-registration was evaluated using phantom studies. To approximate clinical dual-headed SPET studies, a Hoffman brain phantom was filled with 99Tcm. For MRI imaging (1.5 Tesla), the phantom was filled with water and doped with Gd-DTPA for contrast enhancement. For both modalities, phantom images were acquired and reconstructed using a routine clinical protocol. MRI and SPET images were matched by Downhill Simplex minimization of the sum of absolute Count Differences (CD), the sum of the Square Root of absolute count differences (SR), the Difference in Shape between the binary masks (SD), the number of Sign Changes in the subtracted image (SC), the Variance of intensities between corresponding pixels (VAR), the sum of absolute count differences between the 2D- and 3D-Gradient images (2DG-3DG) and, finally, the standard deviation of the Uniformity Index (UI), that is the intensity ratio between spatially corresponding voxels. Six degrees of freedom were allowed (three translation and three rotation parameters, three scaling parameters were constrained). The accuracy of the matching process with these different similarity measures was evaluated via the residual mismatch between external markers. We found that CD, SR, VAR nad UI give the most accurate registration compared with the other similarity measures. For the evaluation of SPET-SPET co-registration, five 99Tcm-ECD brain perfusion SPET scans were performed with a dual-headed gamma camera. These studies were then manually misaligned, and subsequently re-aligned using the methods outlined above. For this application, CD, SR and VAR were also found to give the most accurate registration. For all of these algorithms, the computing time required was clinically acceptable (i.e. less than 10 min).

Dynamic SPET parameters of 123I-MIBG cardiac imaging.

Early dynamic and late 123I-MIBG SPET studies were performed to investigate several parameters used to distinguish the characteristics of various cardiac disorders. Forty-six individuals (34 non-diabetic, 12 diabetic) with or without heart disease were included in the study. Early dynamic and late static SPET images were acquired using a triple-headed gamma camera. After selecting mid-sections from vertical (VLA) and horizontal (HLA) long-axis images, regions of interest were created over the apex, whole heart and anterior, inferior, septal and lateral walls of the heart. Various uptake ratios at 3, 11 and 19 min and 4 h after injection (HU3, HU11, HU19, DUP) and clearances (Kse: between HU3 and HU11; Ke: between HU11 and HU19; Kd: between HU19 and DUP) were calculated. There were significant differences among various cardiac pathologies on the delayed images. Cardiomyopathy patients showed the lowest uptake on the delayed images. When all segments in normal patients and all involved segments in myocardial infarcted patients were compared, there was significantly lower uptake of MIBG in infarcted segments at all time points. Kd showed the lowest value compared with Kse and Ke. In cardiomyopathy patients, Kse, Ke and Kd were significantly different from each other. Both Kse and Ke were significantly higher in cardiomyopathy patients than in normal patients. In conclusion, the results of this study are in line with published data and precise measurement of uptake and clearance was possible when excluding background and blood pool activity.

Myocardial SPET imaging with Myoview

Myocardial SPET imaging with Myoview

Quantitative assessment of regional dysfunction from gated single photon emission tomography myocardial perfusion studies: a non-segmental approach.

We present a modified (non-segmental) method for quantification of regional left ventricular dysfunction using gated myocardial perfusion SPET. Gated SPET is increasingly used to obtain complementary information on local perfusion and to assess the relevance of deficits in segmental count densities (attenuation vs perfusion deficit). The non-segmental approach was motivated by a hypothetical limitation regarding the validity of commonly used methods of quantitative wall thickening (WT) analysis. These methods are all based on segmental analysis, which could cause underestimation of 'true' contractile dysfunction in perfusion defects that do not have a strict segmental distribution. SPET images gated in eight time bins 60 min after the injection of 740 MBq 99Tcm-tetrofosmin or 99Tcm-sestamibi were recorded on a triple-headed camera in 20 normal subjects and in 16 patients within 2 weeks and again 3 months after myocardial infarction. Normal limits of wall thickening, calculated from pooled wall thickening profiles obtained in normal subjects, were used to identify and quantify areas with abnormal wall thickening in patients with coronary artery disease. The method was validated against data obtained from contrast ventriculography (CVG) and tested for reproducibility. The reproducibility of the method was excellent: r = 0.98 (WTsev measure 1 = 1.03WTsev measure 2 - 0.01). The localization of wall thickening abnormalities detected by gated SPET correlated well with the localization of regions with abnormal wall motion (WM) identified by CVG. The severity of the regional myocardial dysfunction assessed by gated SPET was closely correlated with the severity of the regional myocardial dysfunction derived from CVG: r = 0.85 (WMsev = 2.55WTsev + 2.30). Furthermore, a good correlation between the total wall thickening severity score and the global left ventricular ejection fraction (LVEF) was observed early and late after myocardial infarction: r = 0.80 (WTsev = -0.4LVEF + 0.46). We conclude that quantitative analysis of regional wall thickening assessed from gated SPET myocardial perfusion scintigraphy is a reliable parameter for regional ventricular function. Categorizing wall thickening abnormalities quantitatively may be helpful in assessing small changes in regional function that may occur between sequential gated SPET images.

Evaluation of the mutual information cost function for registration of SPET and MRI images of the brain

Evaluation of the mutual information cost function for registration of SPET and MRI images of the brain

99Tcm-Neurolite brain SPET imaging as an outcome predictor after brain trauma

99Tcm-Neurolite brain SPET imaging as an outcome predictor after brain trauma

Planar versus SPET imaging in the assessment of condylar growth

Planar versus SPET imaging in the assessment of condylar growth