Design and implementation of an automated partial volume correction in PET: application to dopamine receptor quantification in the normal human striatum

The considerable effort and potential lack of reproducibility of human-driven PET quantification and partial volume correction (PVC) can be alleviated by use of atlas-based automatic analysis. The present study examined the application of a new algorithm designed to automatically define 3-dimensional regions of interest (ROIs) and their effect on dopamine receptor quantification in the normal human brain striatum, both without and with PVC. Methods: A total of 90 healthy volunteers (age range, 18-46 y) received a single injection of (11)C-raclopride, and automatic segmentation of concomitant structural MR images was performed using a maximum-probability atlas in combination with a trained neural network. For each identified tissue segment considered homogeneous for the tracer (or volumes of interest [VOIs]), an a priori criterion based on minimum axial recovery coefficient (RC(zmin) = 50%, 75%, and 90%) was used to constrain the extent of each ROI. RESULTS: With ROIs essentially overlapping the entire VOI volume (obtained with RC(zmin) = 50%), the binding potential (BP(ND)) of (11)C-raclopride was found to be around 2.2 for caudate and 2.9 for putamen, an underestimation by 35% and 28%, respectively, according to PVC values. At increased RC(zmin), BP(ND) estimates of (11)C-raclopride were increased by 12% and 21% for caudate and 8% and 15% for putamen when the associated ROIs decreased to around 65% and 43% of total tissue volume (VOI) for caudate and 67% and 31% for putamen. After PVC, we observed relative increases in BP(ND) variance of 12% for caudate and 20% for putamen, whereas estimated BP(ND) values all increased to 3.4 for caudate and 4.0 for putamen, regardless of ROI size. Dopamine receptor concentrations appeared less heterogeneous in the normal human striatum after PVC than they did without PVC: the 25%-30% difference in BP(ND) estimates observed between caudate and putamen remained significant after PVC but was reduced to slightly less than 20%. Furthermore, the results were comparable with those obtained with a manual method currently in use in our laboratory. CONCLUSION: The new algorithm allows for traditional PET data extraction and PVC in an entirely automatic fashion, thus avoiding labor-intensive analyses and potential intra- or interobserver variability. This study also offers the first, to our knowledge, large-scale application of PVC to dopamine D(2)/D(3) receptor imaging with (11)C-raclopride in humans.     

Assessment of global cardiac I-123 MIBG uptake and washout using volumetric quantification of SPECT acquisitions

Background

Assessment of cardiac innervation using single-photon emission computer tomography (SPECT) is less established than planar imaging, but may be more suitable for quantification. Therefore, a volumetric quantification of I-123 MIBG SPECT acquisitions was performed. Reproducibility, the effects of extra cardiac I-123 MIBG uptake and the relation with conventional planar indices were evaluated.

Methods

54 patients referred for planar and SPECT I-123 MIBG acquisitions were included. Ellipsoidal or box-shaped volumes of interest were placed on the left ventricle, cardiac lumen, mediastinum, lung and liver. SPECT segmentation was performed twice in all patients. Indices were determined based on the heart-to-mediastinum (HM), myocardial wall-to-mediastinum and myocardial wall-to-lumen regions. HM ratios and washout rates were also determined based on anterior planar images.

Results

Cardiac count densities were highly reproducible (CV 1.5-5.4, ICC 0.96-0.99) and inter-rater variability was low (CV 1.8-6.8, ICC 0.94-0.99). Mediastinal uptake was an important explanatory variable of uptake in the entire heart (early R ²?=?0.36; delayed R ² =0.43) and myocardial wall (early R ²?=?0.28; delayed R ²?=?0.37). Lung washout was an explanatory variable of organ washout of the heart (heart R ²?=?0.38; myocardial wall R ²?=?0.33). In general, SPECT indices showed moderate-to-good correlations with the planar uptake (PCC 0.497-0.851).

Conclusion

By applying a volumetric segmentation method we were able to segment the heart in all patients. SPECT I-123 MIBG quantification was found to be highly reproducible and had a moderate to good correlation with the planar indices.     

Diagnostic performance of a 3-D automated quantification method of dopamine D2 receptor SPECT studies in the differential diagnosis of parkinsonism

BACKGROUND: Assessment of post-synaptic D2 receptors with 123I-IBZM SPECT is helpful in distinguishing idiopathic (IPS) from other parkinsonian syndromes (non-IPS). AIM: To evaluate the diagnostic performance of a recently introduced three-dimensional automated quantification method in a large group of parkinsonian patients. METHODS: IBZM SPECT was performed in 101 consecutive patients with IPS (n = 49) and non-IPS (n = 52). Striatal/frontal cortex binding ratios were assessed by a standard manual quantification method and by the automated method. For the latter patient studies were registered to a mean template of healthy controls (n = 13). IBZM binding was calculated from a 3-D volume-of-interest map established on the normal template. The diagnostic performance of the automated and manual approaches were assessed by receiver operating characteristic (ROC) analyses. RESULTS: Specific striatal binding ratios of both quantification methods showed a close linear relationship (y = 0.81x + 0.1188; R2 = 0.8062). At optimal decision thresholds sensitivity and specificity were 87% and 90% for the automated, and 85% and 90% for the manual method, respectively. The area under the ROC curve was 0.92 for the automated and 0.93 for the manual method, showing no statistical difference. The area under the ROC curve corresponding to a false positive fraction from 0% to 20% was 0.163 for the automated and 0.166 for the manual evaluation. CONCLUSIONS: The diagnostic performance of an automated 3-D quantification method for IBZM SPECT studies has been shown to be equal to, or even better than, a standard manual technique. Advantages of automated quantifications are observer independence and fast processing times. This method may be also used as a platform for processing large data sets/multicentre studies in order to objectively evaluate basal ganglia disorders.     

Dynamic SPECT in two healthy volunteers to determine the optimal time for in vivo D2 dopamine receptor imaging with 123I-IBZM using the rotating gamma camera.

Dynamic SPECT was performed in two healthy male volunteers with a single slice brain dedicated camera (Strichman Medical Equipment 810, first study) and a rotating gamma camera (Siemens Dual Rota ZLC37, second study) to obtain information about the optimal imaging time for the dopamine D2 receptor specific ligand 123I-(S)-(-)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl]-benzamide (123I-IBZM). Count rates in the basal ganglia and in several cerebral cortical regions were used to define specific and aspecific binding, respectively. On the basis of the first study, 90-150 min seemed the optimal time for rotating gamma camera 123I-IBZM-SPECT. On the basis of the second study the optimal period was considered to be 60-120 min. It is recommended to apply the same imaging time after injection in a protocol to all patients and volunteers as otherwise a comparison may not be reliable.     

Heuristic optimization algorithms applied to the quantification of spectroscopic data

The quantification of in vivo MR spectra imposes severe problems because of low spectral resolution and poor signal-to-noise ratio. Maximum likelihood methods are often applied. However, with conventional spectrum analysis procedures, the search for a global minimum in a multidimensional space often terminates in only a local minimum. Heuristic optimization procedures are able to circumvent this difficulty. Two approaches, the genetic algorithm and the simulated annealing, have been adapted to the quantification of MR spectra. For evaluation purposes, the procedures have been applied to synthetic and in vivo spectra with different noise levels. They both allowed a reliable spectrum quantification. The areas of most peaks were quantified reproducibly, although in some cases, the discrimination between spectroscopically almost identical metabolites (e.g., glutamate and glutamine) was not completely satisfactory. The two algorithms are found to be valuable alternative methods in the quantification of in vivo MR spectra.     

Dopamine D2 receptor SPECT imaging: Basicin vivo characteristics and clinical applications of123I-IBZM in humans

The purposes of this study are to evaluate the utility of kit formulation, the basicin vivo characteristics, and clinical usefulness of dopamine D₂ receptor imaging with¹²³I-(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrodinyl)methyl]-benzamide (¹²³I-IBZM). We studied 22 normal controls, 3 early symptomatic Huntington’s disease patients, and 1 patient with visual hallucination on and off neuroleptics.¹²³I-IBZM could be conveniently prepared with a high degree of purity from a kit, but with relatively low radiochemical yield. We demonstrated¹²³I-IBZM receptor binding equilibrium by performing serial SPECT scanning in a normal volunteer. The basal ganglia/frontal cortex (BG/FC) ratios plateaued after the specific binding reached equilibrium approximately 60 minutes after injection. The BG/FC ratio declined significantly with age. The ratios for the Huntington’s disease patients were significantly lower than those for normal controls. The images of the patient off neuroleptic therapy showed dramatically increased BG activity compared with those obtained while on therapy. The BG/FC ratio provides an estimate of B_max/K_d and hence the receptor density. It appears important to perform SPECT early in the equilibrium phase and at a fixed time after injection to obtain significantly high signal to noise ratios.¹²³I-IBZM is an ideal tracer for SPECT including a rotating gamma camera type which can provide estimates of the receptor density objectively by calculating the BG/FC ratio, and is a promising agent for the investigation of dopamine D₂ receptors in clinical conditions.     

SPECT imaging of dopamine D2 receptors with 123I-IBZM: initial experience in controls and patients with Parkinson's syndrome and Wilson's disease.

123I-(S-)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl]-benzamide (123I-IBZM) is a highly selective CNS D2 dopamine receptor ligand suitable for SPECT. This study reports on IBZM-SPECT findings in 60 patients including eight controls and 52 patients presenting with disorders of the dopaminergic system, including idiopathic Parkinson's syndrome (IPS) (n = 18), Parkinson's syndromes of other aetiology (PS) (n = 24) and Wilson's disease (n = 10). SPECT was performed 2 h p.i. of 185 MBq 123I-IBZM. For semiquantitative evaluation basal ganglia to frontal cortex ratios (BG/FC ratios) were calculated. In controls BG/FC ratios of 1.55 +/- 0.05 S.D. were observed. Findings in IPS patients (BG/FC ratio: 1.51 +/- 0.05) were not different from controls. In PS patients striatal IBZM binding (BG/FC ratio: 1.35 +/- 0.11) was significantly (P less than 0.001) lower compared to the control and IPS groups. Asymptomatic patients with Wilson's disease presented normal IBZM binding. In those with neurologic symptoms IBZM fixation was markedly reduced. IBZM-SPECT has shown to be a suitable means for in vivo imaging of striatal dopamine D2 receptors in controls and various disorders of the dopaminergic system. Our preliminary data suggest that IBZM-SPECT is potentially useful for discriminating between IPS and PS (sensitivity: 100%; specificity: 83%). In patients with Wilson's disease IBZM accumulation seems to correlate with the presence of neurologic symptoms.     

The principles of quantification applied to in vivo proton MR spectroscopy

Following the identification of metabolite signals in the in vivo MR spectrum, quantification is the procedure to estimate numerical values of their concentrations. The two essential steps are discussed in detail: analysis by fitting a model of prior knowledge, that is, the decomposition of the spectrum into the signals of singular metabolites; then, normalization of these signals to yield concentration estimates. Special attention is given to using the in vivo water signal as internal reference.     

Functional morphometry of the striatum in Parkinson's disease on three-dimensional surface display of 123I-beta-CIT SPECT data.

The purpose of this study was to evaluate whether striatal morphology on a three-dimensional surface display of 123I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (123I-beta-CIT) SPECT data can be used as a diagnostic index for Parkinson's disease. METHODS: We studied 11 patients with mild Parkinson's disease and 21 age-matched controls. Triple-head SPECT scans were acquired for 30 min at 20 h after injection of 123I-beta-CIT. We measured the vertical height of the caudate head (H) and the length of the long axis of the striatum (L) on the three-dimensional surface display generated from SPECT data. The morphometric index of the striatum was defined as L/H. The power of L/H to discriminate Parkinson's disease and control groups was evaluated by discriminant function analysis and was compared with that of region of interest (ROI)-based 123I-beta-CIT binding measurements (V"3) and their ratios. RESULTS: The mean L/H ratios (ipsilateral/contralateral) to the most affected limbs were (33%/45%) lower in the Parkinson's disease group compared with the control group, respectively. All other ROI-based measures confirmed that dopamine transporter reductions were most severe in the contralateral posterior putamen (a 68% reduction in V"3). In 1 patient with a subsequent clinical diagnosis of drug-induced parkinsonism, all SPECT measures were normal. The contralateral putamen contributed most to the discriminatory power, and the contralateral L/H showed the best discriminatory power of all SPECT measures. CONCLUSION: These results suggest that striatal morphology on a three-dimensional display of 123I-beta-CIT SPECT data provides information of diagnostic significance for Parkinson's disease. This morphometry can be done without requiring technically demanding ROI analysis, and thus this technique may be suitable for routine clinical use.     

Quantitation of iodine-123-beta-CIT dopamine receptor uptake in a phantom model.

OBJECTIVE: The purpose of this study was to determine the effects of technical factors such as collimation and filtration on the measurement of 123I-beta-CIT uptake in the striatum. METHODS: All SPECT studies were performed using a brain phantom containing striata within a bone- and tissue-equivalent skull. The effects of collimator resolution and septal penetration were assessed from 99mTc and 123I studies containing variable activities in the striata and background regions. Optimum attenuation coefficients (mu) were determined from studies containing uniform activity in the brain. RESULTS: For 99mTc, mu was 0.095 cm-1 and 0.07 cm-1 for parallel-hole and fanbeam collimators, respectively. For 123I, these values dropped to 0.09 cm-1 and 0.00 cm-1 (zero) for medium-energy and fanbeam collimators, respectively. Striatal uptake was significantly underestimated, particularly for medium-energy and general-purpose collimators. With 99mTc, fanbeam collimation gave a 50% increase in the measured striatal uptake, compared to medium-energy collimation. However, with 123I, this gain was eliminated by septal penetration and scatter. Increasing transaxial slice thickness, ROI size and decreasing filter cutoff frequency all degraded apparent striatal uptake. CONCLUSION: Partial volume effects, combined with the averaging effects of increasing slice thickness and ROI size, are the most significant factors affecting measurement of striatal uptake of 123I-beta-CIT. The increased resolution of low-energy high-resolution collimators, compared to a medium-energy collimator, is offset by the increased septal penetration and scatter.     

Prognostic value of automated quantification of 99mTc-sestamibi myocardial perfusion imaging.

Although human interpretation of (99m)Tc-sestamibi SPECT myocardial perfusion imaging has been repeatedly validated in the diagnostic and prognostic assessment of coronary artery disease, it remains unclear if automated computer-derived quantitative indices of perfusion have similar or independent prognostic information. METHODS: We studied 718 patients referred for (99m)Tc-sestamibi SPECT myocardial perfusion imaging who were followed for 5.6 +/- 1.1 y (mean +/- SD). The SPECT studies were initially interpreted visually without benefit of computer-based analysis and were then subjected to a blinded reprocessing to extract quantitative indices of perfusion. Follow-up was through the Manitoba Population Health Research Data Repository. Acute myocardial infarction or cardiac death occurred in 79 individuals (11.0% of the cohort). RESULTS: Visual and quantitative categorization of scan perfusion abnormalities showed similar prognostic value for predicting acute myocardial infarction or cardiac death. Discordance between the visual and quantitative categorizations defined a group at intermediate risk. There was a gradient of risk with increasing severity of the summed stress score (SSS) or summed difference score (SDS). The automated SSS and SDS provided incremental prognostic information over that obtained from visual interpretation. CONCLUSION: Automated quantification of (99m)Tc-sestamibi SPECT myocardial perfusion scans provides objective prognostic information and may complement the conventional visual image interpretation.     

A case of increased 123I-IMP uptake in adenocarcinoma of the lung

It has been reported that delayed 123I-IMP lung scintigraphy shows a defect corresponding to the tumor with increased accumulation around the tumor, and that an increased accumulation is associated with atelectasis and inflammation. We presented a case of increased uptake of 123I-IMP in lung cancer. None of the other reported case of increased uptake in lung cancer, to our knowledge, occurred. A 55-year-old man had a 6 cm mass in the lower lobe of the right lung. Cytologic examination with a small curette diagnosed the case as an adenocarcinoma. The 123I-IMP scintigraphy was performed 24 hours after intravenous injection of 111 MBq of 123I-IMP. The 123I-IMP SPECT lung images showed an area of increased 123I-IMP concentration corresponding to the tumor mass. The patient's subsequent course was characterized by massive pleural effusion caused by extensive invasion to the pleura despite chemotherapy. He died about 2 months after the 123I-IMP scintigraphy. The right lung removed at necropsy confirmed that the area of high 123I-IMP concentration corresponded to the mass, which proved a poorly differentiated adenocarcinoma. One should note that there is an unusual case with high 123I-IMP uptake in lung cancer.     

123I-FP-CIT SPECT imaging of dopamine transporters in patients with cerebrovascular disease and clinical diagnosis of vascular parkinsonism.

The purpose of our study was to prospectively evaluate the striatal uptake of 123I-labeled N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (FP-CIT) and the response to l-dopa therapy in patients with cerebrovascular disease (CVD) who develop clinical symptoms of vascular parkinsonism (VP). METHODS: Twenty consecutive patients who developed VP in the course of CVD were prospectively enrolled in the study. All patients had CT evidence of CVD (17 patients had lacunar infarcts, 3 patients had territorial strokes). The clinical stage of the patients was assessed using the Hoehn and Yahr scale, and the severity of the symptoms was measured using the Unified Parkinson's Disease Rating Scale score. Ten age-matched subjects were used as controls. SPECT was performed 180 min after injection of 185 MBq 123I-FP-CIT using a dual-head gamma-camera. The ratio of the mean specific-to-nonspecific striatal binding for the entire striatum, caudate, and putamen was calculated in all patients and compared with that of controls. Putamen-to-caudate binding ratios were compared as well. The response to therapy was compared between patients with normal and abnormal 123I-FP-CIT binding. RESULTS: No correlation was found between any of the clinical variables and response to therapy in patients with VP. Nine patients had normal striatal 123I-FP-CIT binding with no significant differences in striatal or subregional binding ratios compared with those of the controls. In contrast, 11 patients had significantly diminished striatal binding compared with that of controls (P < 0.001). Subanalyses showed significantly decreased binding in the caudate (P < 0.04 and P < 0.01 for the right and left caudate, respectively), diminished binding in the putamen (P < 0.04 and P < 0.01 for the right and left putamen, respectively), and a decreased putamen-to-caudate ratio on the right side (P < 0.001). The latter ratio was not significant on the left. Two of the 3 patients with territorial strokes had significantly diminished striatal 123I-FP-CIT binding in the hemisphere contralateral to the CT lesion. All 9 patients with normal scan findings had a poor response to L-dopa. Six of 11 patients with abnormal studies had no response to L-dopa, whereas 5 patients had a good response (P < 0.03). CONCLUSION: The diagnosis of VP cannot be accurately confirmed on the basis of clinical features alone because CVD may alter the typical presentation of PD. Functional imaging with 123I-FP-CIT is highly recommended in patients with CVD who develop symptoms of VP to confirm or exclude the existence of nigrostriatal dopaminergic degeneration. Identifying a subset of patients with reduced 123I-FP-CIT binding in the striatum is important for better treatment selection.     

Evaluation of the lung uptake of 123I-IMP by bronchoalveolar lavage

A 67-year-old female with radiation pneumonitis in the right upper lobe underwent lung scanning and bronchoalveolar lavage 4 hours after the intravenous injection of 123I-IMP. The lung scanning showed increased accumulation of 123I-IMP, corresponding with the area of radiation pneumonitis. The ratios of radioactivities of the cellular and noncellular components in the bronchoalveolar lavage fluid to that of the serum, were 27.0 and 0.39, respectively. Our results suggest that 123I-IMP or its metabolites are transported through alveolo-capillary barrier and taken up by free cells in the alveolar space after 123I-IMP has been bound to nonspecific receptor sites in the endothelial cell in the capillary lumen.     

Compensatory uptake of I-123 MIBG in the contralateral adrenal gland after removal of a pheochromocytoma.

The identification of recurrent or residual tumor tissue is sometimes complicated. The authors describe a 53-year-old woman in whom I-123 metaiodobenzylguanidine (MIBG) scintigraphy revealed a pheochromocytoma in the right adrenal gland. After the tumor was removed, the patient's catecholamine levels normalized. At the 3-month follow-up examination, I-123 MIBG scintigraphy did not reveal uptake in the right adrenal region but rather showed uptake in the left adrenal region. The patient's blood pressure remained in the normal range. A third scintigram, obtained 1 year after tumor resection, no longer detected I-123 MIBG accumulation in the left adrenal gland. These findings suggest that compensatory hyperplasia of the left adrenal gland led to enhanced uptake of I-123 MIBG. They also highlight the need for careful follow-up of such patients to distinguish between physiologic and pathologic processes.