Siroos Mirzaei

Analysis of the Metabolic and Structural Brain Changes in Patients With Torture-Related Post-Traumatic Stress Disorder (TR-PTSD) Using 18F-FDG PET and MRI

AbstractMany people exposed to torture later suffer from torture-related post-traumatic stress disorder (TR-PTSD). The aim of this study was to analyze the morphologic and functional brain changes in patients with TR-PTSD using magnetic resonance imaging (MRI) and positron emission tomography (PET).This study evaluated 19 subjects. Thirteen subcortical brain structures were evaluated using FSL software. On the T1-weighted images, normalized brain volumes were measured using SIENAX software. The study compared the volume of the brain and 13 subcortical structures in 9 patients suffering from TR-PTSD after torture and 10 healthy volunteers (HV). Diffusion-weighted imaging (DWI) was performed in the transverse plane. In addition, the 18F-FDG PET data were evaluated to identify the activity of the elected regions.The mean left hippocampal volume for the TR-PTSD group was significantly lower than in the HV group (post hoc test (Bonferroni) P < 0.001). There was a significant difference between the gray matter volume of the patients with TR-PTSD and the HV group (post hoc test (Bonferroni) P < 0.001). The TR-PTSD group showed low significant expansion of the ventricles in contrast to the HV group (post hoc test (Bonferroni) P < 0.001). Diffusion-weighted imaging revealed significant differences in the right frontal lobe and the left occipital lobe between the TR-PTSD and HV group (post hoc test (Bonferroni) P < 0.001).Moderate hypometabolism was noted in the occipital lobe in 6 of the 9 patients with TR-PTSD, in the temporal lobe in 1 of the 9 patients, and in the caudate nucleus in 5 of the 9 patients. In 2 cases, additional hypometabolism was observed in the posterior cingulate cortex and in the parietal and frontal lobes.The findings from this study show that TR-PTSD might have a deleterious influence on a set of specific brain structures. This study also demonstrated that PET combined with MRI is sensitive in detecting possible metabolic and structural brain changes in TR-PTSD.

Fully automated 3D basal ganglia activity measurement in dopamine transporter scintigraphy (Spectalyzer)

ObjectivesSemiquantitative evaluation of tracer uptake in basal ganglia is superior to visual assessment of images in dopamine transporter (DAT) scintigraphy especially in follow-up of the patients. Manual drawing of regions of interest (ROIs) in two-dimensional (2D) transaxial slices of the single photon emission computed tomography (SPECT) datasets leads to a large inter- and intra-reader variability, while being time consuming. Our aim was to investigate a technique that extracts 3D ROIs in a fully automated fashion and thus might provide reproducible user-independent results allowing better follow-up control and large-scale clinical studies.MethodsThe highest activity of 123IFP-CIT is expected in the basal ganglia. The proposed method (Spectalyzer) uses the following steps to localize this maximum and extract the ROIs in 3D: (1) Dithers the SPECT volume to obtain a 3D volume with binary only. (2) Models the obtained point distributions as two multivariate Gaussian distributions and estimated their parameters using the expectation maximization algorithm. (3) Using the original SPECT activity values, thresholding is performed using a fixed percentage of maximum activity as a parameter to obtain the 3D ROIs. (4) A reference volume in the occipital region is automatically found based on the location of the two ROIs. (5) From the 3D ROIs, statistical information like mean and median activity and the volume is extracted, relative to the activity in the reference region. The resulting values are compared with values from manual 2D ROIs. Further validation is performed by means of an anthropomorphic striatal phantom.ResultsThe method was evaluated on 12 SPECT volumes including anthropomorphic striatal phantoms. In all cases the two basal-ganglia were successfully localized and the 3D ROIs estimated, with perfect reproducibility. The obtained values for the mean activity showed the same trend with the values obtained manually and also with the results of the 2D semiautomatic software, but without the substantial inter- and intra-reader variations.ConclusionsThe proposed method is successful in finding the 3D ROIs and performing the subsequent measurements automatically. It is proposed as an automatic reproducible approach for semiquantitative analysis of DAT scintigraphy.

Cardiac 123I-mIBG scintigraphy is associated with freedom of appropriate ICD therapy in stable chronic heart failure patients

AIM Chronic heart failure (CHF) is a life-threatening clinical syndrome, partly due to sudden cardiac death (SCD). Implantable cardioverter defibrillators (ICD) for primary prevention of SCD have improved overall survival of CHF patients. However, a high percentage of patients never receives appropriate ICD therapy. This prospective multicentre study evaluated whether cardiac sympathetic activity assessed by 123I-mIBG scintigraphy could be helpful in selecting patients for ICD implantation. MATERIALS AND METHODS 135 stable CHF subjects (age 64.5±9.3years, 79% male, LVEF 25±6%) referred for prophylactic ICD implantation were enrolled in 13 institutions. All subjects underwent planar and SPECT 123I-mIBG scintigraphy. Early and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO) and late summed scores were calculated. The primary endpoint was appropriate ICD therapy. The secondary endpoint was defined as the combined endpoint of all first cardiac events: appropriate ICD therapy, progression of heart failure (HF) and cardiac death. RESULTS During a median follow-up of 30months (6-68months), 24 subjects (17.8%) experienced a first cardiac event (appropriate ICD therapy [12], HF progression [6], cardiac death [6]). Late H/M ratio and defect size of 123I-mIBG SPECT were not associated with appropriate ICD therapy. However, late H/M ratio was independently associated with the combined endpoint (HR 0.135 [0.035-0.517], p=0.001). Post-hoc analysis showed that the combination of late H/M ratio (HR 0.461 [0.281-0.757]) and LVEF (HR 1.052 [1.021-1.084]) was significantly associated with freedom of appropriate ICD therapy (p<0.001). CONCLUSION 123I-mIBG scintigraphy seems to be helpful in selecting CHF subjects who might not benefit from ICD implantation.

Clinical audit in nuclear medicine.

Background and aim:Clinical governance is important. Clinical audit is part of clinical governance. The aim of this study was to perform a clinical governance exercise, and the reporting arrangements at an independent hospital provided the opportunity to do this over two phases between 1999 and 2002. Six physicians from four different UK National Health Service (NHS) trusts participated. Methods:Reports were shown anonymously to between two and five of the physicians who had not produced the report. Reports with at least one disagreement were reviewed by the group in order to reach concensus as to whether the disagreement was non-sustainable (NS), trivial (T) or non-trivial (NT), the last two, respectively, judged to make an insignificant or potentially significant impact on patient management. Results:In phase 1,239 audits were produced on 83 reports (2.9 per report), and in phase 2, 636 on 137 reports (4.6 per report). In phase 1, 14 (17%) reports attracted at least one disagreement (NS, five; T, four; NT, five). Of 239 audits, there were 20 disagreements of which five were NS. Moreover, nine audits agreed with a report with a NT disagreement, giving 14 suboptimal audits (5.9%). In phase 2, 80 (58%) reports attracted at least one disagreement (NS, 31 (P<0.003 vs phase 1); T, 35 (P<0.001); NT, 14 (P>0.05)). Of 636 audits, there were 153 disagreements, of which 37 were NS (P<0.05 vs phase 1). Twenty-five audits agreed with a report with a NT disagreement, giving 62 suboptimal audits (9.7%) (P>0.05). Overall, 19/220 reports (8.6%) were thought NT, an error rate comparable to reporting elsewhere in radiology. After phase 1, auditors became more aggressive but the quality of auditing tended to decline, as did the quality of reporting (although not significantly). Conclusion:This study provides a useful framework for monitoring performance.

123i-mibg heart-to-mediastinum ratio is influenced by high-energy photon penetration of collimator septa from liver and lung activity

AimThe 123I-metaiodobenzylguanidine (123I-MIBG) late heart-to-mediastinum ratio (H/M) is a well-established prognostic parameter in patients with chronic heart failure (CHF). However, 123I presents imaging problems owing to high-energy photon emission leading to penetration of collimator septa and subsequent reduction in image quality. Most likely this affects the H/M ratio and may subsequently lead to incorrect patient risk classification. In this prospective study we assessed the intrapatient variation in late H/M ratio between low-energy high-resolution (LEHR) and medium-energy (ME) collimators in patients with CHF. Materials and methodsFifty-three patients with CHF (87% male, age 63±8.3 years, left ventricular ejection fraction 29±7.8) referred for 123I-MIBG scintigraphy were enrolled in the study. In each patient, after the administration of 185 MBq 123I-MIBG, early (15 min after injection) and late (4 h after injection) planar anterior thoracic images were acquired with both LEHR and ME collimators. Early and late H/M ratios were calculated on the basis of the mean count densities from the manually drawn regions of interest (ROIs) over the left ventricle and a predefined fixed ROI placed in the upper mediastinum. Additional ROIs were drawn over the liver and lungs. Liver/lung to myocardium and liver/lung to mediastinal ratios were calculated to estimate the effect of collimator septa penetration from liver and lung activity on the myocardial and mediastinal ROIs. ResultsThe mean LEHR collimator-derived parameters were lower compared with those from the ME collimator (late H/M 1.41±0.18 vs. 1.80±0.41, P<0.001). Moreover, Bland–Altman analysis showed that with increasing late H/M ratios the difference between the ratios from the two collimator types increased (R2=0.73, P=0.001). Multivariate regression analysis showed that almost 90% of the variation in the difference between ME and LEHR late H/M ratios could be explained by scatter from the liver in both the mediastinal and myocardial ROIs (R2=0.90, P=0.001). Independent predictors for the difference in the late H/M between ME and LEHR were the liver-to-heart ratio and the liver-to-mediastinum ratio assessed by ME (standardized coefficient of −1.69 and 1.16, respectively) and LEHR (standardized coefficient of 1.24 and −0.90, respectively) (P<0.001 for all). ConclusionIntrapatient comparison in H/M between the ME and LEHR collimators in patients with CHF showed that with increasing H/M the difference between the ratios increased in favour of the ME collimator. These differences could be explained by septal penetration of high-energy photons from both the liver and the lung in the mediastinum and myocardium, being lowest when using the ME collimator. These results strengthen the importance of the recommendation to use ME collimators in semiquantitative 123I-MIBG studies.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

Objective: Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of 99mTc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with 177Lu-DOTATATE used for PRRT. Methods: 8 patients (4 women, 4 men, age range 46–76 years) with histologically proven NETs, who showed high SR loads by 99mTc-EDDA/HYNIC-TOC scintigraphy, were treated with 177Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. Results: All patients demonstrated 177Lu-DOTATATE accumulation in all lesions previously detected by 99mTc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. Conclusions: SPECT-CT after 177Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using 99mTc-EDDA/HYNIC-TOC. This could reflect the broader affinity of 177Lu-DOTATATE for SRs compared with 99mTc-EDDA/HYNIC-TOC.

Easy-to-use online software package for internal dose assessment after radionuclide treatment in clinical routine.

Background Internal dose assessment after radionuclide therapy is usually performed using home-made software packages. The dose assessment includes image registration, region-of-interest drawing, time-activity curve generation, and manual calculation of residence times followed by dose calculation with the OLINDA/MIRD software. The drawback of these methods is that several steps have to be performed using various software products possibly installed on different workstations. The aforementioned approaches are error-prone as well as difficult and time-consuming. In this article, we present a commercial software package that implements all the required dose calculation steps in 1 application, which greatly facilitates the internal dose assessment. Methods and Results The workflow of the newly developed software package “Hybrid Dosimetry” proceeds from automatic image registration to region-of-interest drawing, followed by time-activity curve fitting and dose calculation according to the MIRD method. The software is available online and can be run on independent computers using images in the common DICOM format. We used the package for internal dosimetry of 8 patients treated with 177Lu-DOTATATE and compared the results with manual dose calculation. Conclusions The online software package presented is platform independent and allows fast dose calculations. The results obtained with the new package were in perfect agreement with manual methods.

Scientific computing with Java

In this work we aimed to use examples from various fields (physics, medicine and structural biology) and several mathematical libraries for Java (COLT and JLAPACK) to demonstrate the advantages of scientific computing using Java. We also compared the runtimes of different Java compilers (Sun, IBM and Blackdown) and found that IBMs Java compiler results in the smallest CPU time.

Metabolic Pattern of Asymptomatic Hip-Prosthesis by 18F-FDG-Positron-Emission-Tomography.

Background: Joint replacement is a procedure with a major impact on the quality of life of patients with joint degenerative disease or traumatic injuries. However, some patients develop symptoms after the intervention caused by mechanical loosening or infection. Metabolic imaging by 18F-FDG-PET investigated in these patients isoften hampered by low specificity for diagnosis of possible septic vs. mechanical loosening. The reason for this shortcoming is to our opinion the unawareness of physiological remodeling processes that could be seen in asymptomatic patients. Objectives: In order to overcome this drawback, we aimed to find out the physiological metabolic functional pattern in asymptomatic patients with implanted hip prosthesis Patients and Methods: Twelve patients (6 males, 6 females); mean age 73 ± 7 (range 58 - 91) years were prospectively enrolled in the study. The patients were admitted to our department for oncological referral with implanted hip prostheses. All patients explained no symptoms with regard to their implanted prosthesis. The attenuation corrected images were used for analysis. Results: Fourteen hip prostheses in 12 patients were visually analyzed. Seven out of 14 prostheses among 12 patients showed focal periprosthetic enhanced metabolism, two of which showed two sites of enhanced uptake; whereas, the remaining five prostheses showed singular hypermetabolic areas within the periprosthetic site. The remaining seven prostheses in the other five patients showed no periprosthetic-enhanced uptake. Conclusion: Of the asymptomatic patients investigated, 58% showed focal enhanced periprosthetic glucose metabolism. This finding should be taken into consideration as a more probable unspecific metabolic pattern for correct interpretation of 18F-FDG-PET studies in patients with suspected septic loosening of the hip prosthesis.

Improvement of Cerebral Hypoperfusion with Levothyroxine Therapy in Hashimoto's Encephalopathy Demonstrated by 99mTc-HMPAO-SPECT

Background: Hashimotos encephalopathy (HE) is a rare immune-mediated encephalopathy associated with autoimmune Hashimotos thyroiditis. Objectives and Methods: We report on a patient with HE and significant clinical improvement correlating with an increase in cerebral blood flow demonstrated by hexamethylpropyleneamine oxime (HMPAO) single-photon emission computed tomography (SPECT). HMPAO-SPECT was performed with 740 MBq of technetium-99m-HMPAO. To demonstrate the improvement in regional cerebral blood flow, individual regions of interest were drawn around visually diminished HMPAO uptake, the lesion to reference region ratio was calculated and transverse section images and semi-quantitative measurements were performed. Results: We show a 5-year follow-up with significant clinical improvement, a 10-fold reduction in autoantibodies to thyroid peroxidase and an approximately 20% improvement in cerebral blood flow with HMPAO-SPECT. Conclusion: Adequate levothyroxine treatment achieving and maintaining euthyroidism should be considered as therapy to lower autoantibodies and improve clinical outcome in patients with Hashimotos thyroiditis and encephalopathy.