High-density electric source imaging patterns and outcomes following temporal lobectomy in patients with hippocampal sclerosis.

OBJECTIVE: The objective of this study was to ascertain specific patterns of electrical source imaging (ESI) that are associated with a good surgical outcome (no seizure recurrence) using 256-channel high-density (HD) electroencephalography (EEG) in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) who underwent temporal lobectomy. METHODS: Adult patients (age ≥ 18 years) were prospectively recruited from September 2016 to May 2020 at the authors' center. All patients underwent phase I presurgical evaluation and were subsequently advised to proceed with surgery based on consensus from a multidisciplinary epilepsy conference, without knowing HD-ESI results. All recruited patients were followed for at least 12 months after surgery. The outcome of interest was a status of no seizure recurrence, which was assessed at the end of the study. The association between ESI patterns and outcome was assessed using the chi-square or Fisher exact test. Associated p values as well as odds ratios and 95% CIs were reported. The diagnostic performance of the significant pattern associated with the outcome was also evaluated. RESULTS: Fifty-eight patients with known predictors for either good or worse surgical outcomes were recruited. The mean postoperative follow-up period was 33.34 (SD 13.88) months. Forty-seven patients had sufficient interictal epileptiform discharges for HD-ESI analysis. Thirteen of these 47 patients experienced seizure recurrence. The most common source localizations were at Brodmann area (BA) 20 (inferior temporal area) and BA 21 (middle temporal area). A specific ESI pattern of BA 21 without extratemporal sources was significantly associated with no seizure recurrence (p = 0.047). This pattern had a high positive predictive value of 100% and false-positive rate of 0% associated with no seizure recurrence following the surgery. CONCLUSIONS: A specific ESI pattern that was highly associated with no seizure recurrence following surgery was demonstrated by a 256-channel HD-EEG. If this pattern can be reproducibly proven in further studies, some TLE-HS patients may be able to proceed with surgery without further investigations.

Serum proinsulin levels as peripheral blood biomarkers in patients with cognitive impairment.

Insulin has long been associated with dementia. Insulin affecting the clearance of amyloid-ß peptide and phosphorylation of tau in the CNS. Proinsulin is a precursor of insulin and its elevated serum levels are associated with peripheral insulin resistance that may reduce brain insulin levels. Our study aimed to assess differences in serum proinsulin levels between normal and cognitive impairment groups. Prospective recruitment of elderly participants was initiated from October 2019 to September 2023. Patients were divided into "cognitive impairment" and "normal cognition" group. All participants had blood drawn and serum proinsulin was measured at baseline and 12 months. Neurocognitive testing was performed every 6 months. A total of 121 participants were recruited. Seventy-seven were in the normal cognition group and 44 in the cognitive impairment group. The glycemic control and prevalence of diabetes type 2 was similar between groups. Baseline serum proinsulin levels were higher in the cognitively impaired group compared to the normal group at baseline (p = 0.019) and correlated with worse cognitive scores. We identified cognitive status, age, and BMI as potential factors associated with variations in baseline proinsulin levels. Given the complex interplay between insulin and dementia pathogenesis, serum biomarkers related to insulin metabolism may exhibit abnormalities in cognitive impaired patients. Here we present the proinsulin levels in individuals with normal cognitive function versus those with cognitive impairment and found a significant difference. This observation may help identifying non-diabetic patients suitable for treatment with novel AD drugs that related to insulin pathway.

Prospective evaluation of plasma phosphorylated tau in a real-life memory clinic in Thailand.

INTRODUCTION: Despite the substantial accuracy of plasma p-tau in diagnosing Alzheimer's disease (AD) in research cohorts, data on real-life memory clinic patients are lacking. METHODS: Memory clinic patients at their early symptomatic stages were prospectively enrolled to undergo routine clinical assessment, plasma p-tau181 quantification (Simoa), amyloid and tau-positron emission tomography (PET). The diagnostic performance of plasma p-tau181, neurocognitive specialists, and regional tau-PET were compared head-to-head using amyloid-PET as the reference standard. RESULTS: Plasma p-tau181 has the area under the curve (AUC), sensitivity, specificity, and accuracy of 0.84 (95% confidence interval [CI] 0.73-0.94), 0.80 (95% CI 0.64-0.90), 0.75 (95% CI 0.51-0.90), and 0.78 (95% CI 0.65-0.88) for detecting amyloid-PET positivity in early symptomatic patients, respectively. The AUC of clinical diagnosis and tau-PET were 0.70 (95% CI 0.56-0.85) and 0.88 (95% CI 0.79-0.97), respectively. DISCUSSION: Plasma p-tau181 also performed well in real-life memory clinic settings and its role in clinical practice is supported.

Brain perfusion single photon emission computed tomography abnormality in MRI-negative stroke-like patients post COVID-19 vaccination.

Stroke-like symptoms after COVID-19 vaccination was thought to be functional if there was no anatomical image abnormality. We aimed to analyze brain perfusion changes in these patients. A case-control study of brain perfusion single photon emission computed tomography (SPECT) of 12 vaccinated patients with left-sided stroke-like symptoms were compared with 12 age- and gender-matched normal interictal brain SPECTs using voxel-based analysis. Significant hyperperfusion was seen on the right side in postcentral, inferior parietal, mid temporal, parahippocampal, and caudate regions, and on the left side in the thalamus, hippocampus, and mid temporal areas. In addition, there were hypoperfused bilateral superior frontal gyri and right mid/posterior cingulate cortex (Family-wise-error corrected p-values  < .05). Both hypoperfusion and hyperperfusion in the brain are demonstrated. We hypothesize that these findings might be the result of the functional neurological disorder. However, based on other previous studies, circulating spike protein in the patients' plasma early after vaccination might also be the cause.

Brain laterality evaluated by F-18 fluorodeoxyglucose positron emission computed tomography in autism spectrum disorders.

Background and rationale: Autism spectrum disorder (ASD) is a neuropsychiatric disorder that has no curative treatment. Little is known about the brain laterality in patients with ASD. F-18 fluorodeoxyglucose positron emission computed tomography (F-18 FDG PET/CT) is a neuroimaging technique that is suitable for ASD owing to its ability to detect whole brain functional abnormalities in a short time and is feasible in ASD patients. The purpose of this study was to evaluate brain laterality using F-18 FDG PET/CT in patients with high-functioning ASD. Materials and methods: This case-control study recruited eight ASD patients who met the DSM-5 criteria, the recorded data of eight controls matched for age, sex, and handedness were also enrolled. The resting state of brain glucose metabolism in the regions of interest (ROIs) was analyzed using the Q.Brain software. Brain glucose metabolism and laterality index in each ROI of ASD patients were compared with those of the controls. The pattern of brain metabolism was analyzed using visual analysis and is reported in the data description. Results: The ASD group's overall brain glucose metabolism was lower than that of the control group in both the left and right hemispheres, with mean differences of 1.54 and 1.21, respectively. We found statistically lower mean glucose metabolism for ASD patients than controls in the left prefrontal lateral (Z = 1.96, p = 0.049). The left laterality index was found in nine ROIs for ASD and 11 ROIs for the control. The left laterality index in the ASD group was significantly lower than that in the control group in the prefrontal lateral (Z = 2.52, p = 0.012), precuneus (Z = 2.10, p = 0.036), and parietal inferior (Z = 1.96, p = 0.049) regions. Conclusion: Individuals with ASD have lower brain glucose metabolism than control. In addition, the number of ROIs for left laterality index in the ASD group was lower than control. Left laterality defects may be one of the causes of ASD. This knowledge can be useful in the treatment of ASD by increasing the left-brain metabolism. This trial was registered in the Thai Clinical Trials Registry (TCTR20210705005).

A Novel method of seizure onset zone localization by serial Tc-99 m ECD brain perfusion SPECT clearance patterns.

In this prospective study, we postulate that there is a difference between clearance of [99mTc]Tc- ethyl cysteinate dimer (ECD) in the seizure onset zone (SOZ) and other brain areas and thus SOZ localization by clearance patterns might become a potential novel method for SOZ localization in epilepsy. The parametric images of brain ECD clearance were generated by linear regression model analysis from serial brain SPECT scans from 30 to 240 min after ECD injection (7-times point) in 7 patients with drug-resistant epilepsy and 3 normal volunteers. Clearance patterns of the SOZ confirmed by good surgical outcome or consensus with other investigations were analyzed quantitatively and semi-quantitatively by visual grading (slower or faster washout than contralateral brain regions). The average [99mTc]Tc-ECD clearance rates of SOZs were + 1.08% ± 2.57%/hr (wash in), -7.02% ± 2.56%/hr (washout), and -5.37% ± 1.71%/hr (washout) in ictal, aura and interictal states, respectively. Paired t-tests between the SOZ and contralateral regions showed statistically significant difference (p = 0.039 in interictal state). Clearance patterns that can define the SOZs were 1) wash in and slow washout on ictal slope, 2) fast washout on aura slope and interictal slope with 100% (6/6), 100% (2/2) and 75% (6/8) localization using ictal, aura, and interictal slope maps, respectively. Our study provided the evidence that clearance pattern methods are potential additive diagnostic tools for SOZ localization when routine one-time point SPECT are unable to define the SOZ.

Cutaneous Management after Extravasation of High-Concentrated Amino Acid Solution Administered for Renal Protection in PRRT.

High-concentrated amino acid solution is used to protect the kidneys during peptide receptor radionuclide therapy (PPRT) in patients with neuroendocrine tumors (NETs). Extravasation of the solution can cause cutaneous complications. In this study, we described a 66-year-old man with metastatic medullary thyroid cancer and a 32-year-old woman with metastatic pancreatic NET who developed cutaneous lesions caused by the extravasation of an amino acid solution (25 g of lysine and 25 g of arginine in 1 L of normal saline) during PRRT with [177Lu]Lu-DOTA-TATE. Both were treated conservatively, and these cutaneous lesions gradually improved. The patient with metastatic pancreatic NET rejected the amino acid infusion in subsequent cycles of PRRT and therefore received [177Lu]Lu-DOTA-TATE alone, and her serum creatinine level and estimated glomerular filtration rate (eGFR) remained normal for 2 months after the last treatment. These two cases revealed cutaneous complications resulting from high-concentrated amino acid solution during PRRT because of hyperosmolarity. Health care providers should be aware of this complication to ensure its prevention and appropriate management. Preserved renal function was demonstrated after [177Lu]Lu-DOTA-TATE treatment in the absence of the infusion of a high-concentrated amino acid solution. However, long-term follow-up of renal function is suggested.

Prolonged migraine aura resembling ischemic stroke following CoronaVac vaccination: an extended case series.

BACKGROUND: After the initiation of the COVID-19 vaccination program in Thailand, thousands of patients have experienced unusual focal neurological symptoms. We report 8 patients with focal neurological symptoms after receiving inactivated virus vaccine, CoronaVac. CASE SERIES: Patients were aged 24-48 years and 75% were female. Acute onset of focal neurological symptoms occurred within the first 24 h after vaccination in 75% and between 1-7d in 25%. All presented with lateralized sensory deficits, motor deficits, or both, of 2-14 day duration. Migraine headache occurred in half of the patients. Magnetic resonance imaging of the brain during and after the attacks did not demonstrate any abnormalities suggesting ischemic stroke. All patients showed moderately large regions of hypoperfusion and concurrent smaller regions of hyperperfusion on SPECT imaging while symptomatic. None developed permanent deficits or structural brain injury. DISCUSSIONS: Here, we present a case series of transient focal neurological syndrome following Coronavac vaccination. The characteristic sensory symptoms, history of migraine, female predominant, and abnormal functional brain imaging without structural changes suggest migraine aura as pathophysiology. We propose that pain related to vaccine injection, component of vaccine, such as aluminum, or inflammation related to vaccination might trigger migraine aura in susceptible patients.

Nuclear imaging for localization and surgical outcome prediction in epilepsy: A review of latest discoveries and future perspectives.

Background: Epilepsy is one of the most common neurological disorders. Approximately, one-third of patients with epilepsy have seizures refractory to antiepileptic drugs and further require surgical removal of the epileptogenic region. In the last decade, there have been many recent developments in radiopharmaceuticals, novel image analysis techniques, and new software for an epileptogenic zone (EZ) localization. Objectives: Recently, we provided the latest discoveries, current challenges, and future perspectives in the field of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in epilepsy. Methods: We searched for relevant articles published in MEDLINE and CENTRAL from July 2012 to July 2022. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis was conducted using the keywords "Epilepsy" and "PET or SPECT." We included both prospective and retrospective studies. Studies with preclinical subjects or not focusing on EZ localization or surgical outcome prediction using recently developed PET radiopharmaceuticals, novel image analysis techniques, and new software were excluded from the review. The remaining 162 articles were reviewed. Results: We first present recent findings and developments in PET radiopharmaceuticals. Second, we present novel image analysis techniques and new software in the last decade for EZ localization. Finally, we summarize the overall findings and discuss future perspectives in the field of PET and SPECT in epilepsy. Conclusion: Combining new radiopharmaceutical development, new indications, new techniques, and software improves EZ localization and provides a better understanding of epilepsy. These have proven not to only predict prognosis but also to improve the outcome of epilepsy surgery.

Impact of reconstruction parameters on lesion detection and localization in joint ictal/inter-ictal SPECT reconstruction.

PURPOSE: Previously, a joint ictal/inter-ictal SPECT reconstruction was proposed to reconstruct a differential image representing the change of brain SPECT image from an inter-ictal to an ictal study. The so-called joint method yielded better performance for epileptic foci localization than the conventional subtraction method. In this study, we evaluated the performance of different reconstruction settings of the joint reconstruction of ictal/inter-ictal SPECT data, which creates a differential image showing the difference between ictal and inter-ictal images, in lesion detection and localization in epilepsy imaging. METHODS: Differential images reconstructed from phantom data using the joint and the subtraction methods were compared based on lesion detection performance (channelized Hotelling observer signal-to-noise ratio (SNRCHO) averaged across four lesion-to-background contrast levels) at the optimal iteration. The joint-initial method which was the joint method that was initialized by the subtraction method at optimal iteration was also used to reconstruct differential images. These three methods with respective optimal iteration and the subtraction method with four iterations were applied to epileptic patient datasets. A human observer lesion localization study was performed based on localization receiver operating characteristic (LROC) analysis. RESULTS: From the phantom study, at their respective optimal iteration, the joint method yielded an improvement in lesion detection performance over the subtraction method of 26%, which increased to 145% when using the joint-initial method. From the patient study, the joint-initial method yielded the highest area under the LROC curve as compared with those of the joint and the subtraction methods with optimal iteration and with 4 iterations (0.44 vs 0.41, 0.39 and 0.36, respectively). CONCLUSIONS: In lesion detection and localization, the joint method at optimal iteration outperformed the subtraction method at optimal iteration and at iteration typically used in clinical practice. Furthermore, initialization by the subtraction method improved the performance of the joint method.

Alterations of regional cerebral glucose metabolism using18F-fluorodeoxyglucose positron-emission tomography/computed tomography and electroencephalography analysis during mindfulness breathing in Anapanasati meditation: A preliminary analysis.

Anapanasati is a core meditation of a breath-centered practice in the Buddhist Theravada tradition, which may have some neurological mechanism effects on the brain. To gain insight into the neurological mechanisms involved in Anapanasati meditation, we measured the alterations of regional cerebral glucose metabolism during Anapanasati meditation using positron-emission tomography/computed tomography (PET/CT) and electroencephalography (EEG) analysis. This prospective study was conducted in six right-handed volunteer participants (two men, four women; aged: 32-67 years) who underwent18F-fluorodeoxyglucose (18F-FDG) PET/CT scans to compare the alterations of regional cerebral glucose metabolism during normal consciousness and Anapanasati meditation states. Spectral EEG analysis was performed throughout the investigations. Statistical parametric mapping was used for the18F-FDG PET/CT image analyses. The visual analysis demonstrated moderate-to-marked increased metabolism in posterior cingulate cortex in all six patients, while mild-to-moderate increased uptake in the whole frontal lobe was also observed in four patients and precuneus in four patients. Meanwhile, the semiquantitative analysis yielded an increase of regional cerebral glucose metabolism in the right mid-to-posterior cingulate gyrus (P < 0.000), with visible alpha waves on the frontal of the EEG findings. Our semiquantitative analysis showed a significantly increased metabolism only in the posterior cingulate cortex, but visually, there was also an increased metabolism in the whole frontal lobe in most of the patients correlating with EEG findings.

Acute prolonged motor aura resembling ischemic stroke after COVID - 19 vaccination (CoronaVac): the first case report.

BACKGROUND: We report the first case of a patient who suffered transient focal neurological deficit mimicking stroke following CoronaVac vaccination. However, instead of an ischemic stroke, motor aura was suspected. CASE PRESENTATIONS: A 24 year-old Thai female presented with left hemiparesis fifteen minutes after receiving CoronaVac. She also had numbness of her left arm and legs, flashing lights, and headaches. On physical examination, her BMI was 32.8. Her vital signs were normal. She had moderate left hemiparesis (MRC grade III), numbness on her left face, arms, and legs. Her weakness continued for 5 days. A brain CT scan was done showing no evidence of acute infarction. Acute treatment with aspirin was given. MRI in conjunction with MRA was performed in which no restricted diffusion was seen. A SPECT was performed to evaluate the function of the brain showing significant hypoperfusion of the right hemisphere. The patient gradually improved and was discharged. DISCUSSIONS: In this study, we present the first case of stroke mimic after CoronaVac vaccination. After negative imaging studies had been performed repeatedly, we reach a conclusion that stroke is unlikely to be the cause. Presumably, this phenomenon could possibly have abnormal functional imaging study. Therefore, we believed that it might be due to cortical spreading depression, like migraine aura, which we had conducted a literature review.

Thai National Guideline for Nuclear Medicine Investigations in Epilepsy.

Epilepsy is a disorder of the brain, which is characterized by recurrent epileptic seizures. These patients are generally treated with antiepileptic drugs. However, more than 30% of the patients become medically intractable and undergo a series of investigations to define candidates for epilepsy surgery. Nuclear Medicine studies using Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) radiopharmaceuticals are among the investigations used for this purpose. Since available guidelines for the investigation of surgical candidates are not up-to-date, The Nuclear Medicine Society of Thailand, The Neurological Society of Thailand, The Royal College of Neurological Surgeons of Thailand, and The Thai Medical Physicist Society has collaborated to develop this Thai national guideline for Nuclear Medicine study in epilepsy. The guideline focuses on the use of brain perfusion SPECT and F-18 fluorodeoxyglucose PET (FDG-PET), the mainly used methods in day-to-day practice. This guideline aims for effective use of Nuclear Medicine investigations by referring physicians e.g. epileptologists and neurologists, radiologists, nuclear medicine physicians, medical physicists, nuclear medicine technologists and technicians.

Clinical association of CXCR4 in primary tumor of papillary thyroid cancer and response to iodine-131 treatment.

OBJECT: Papillary thyroid cancer (PTC) has an excellent prognosis. However, patients with such, if refract to radioiodine treatment, increase recurrent and mortality rates. Tumor aggressiveness in primary tumor of PTC expresses CXCR4 chemokine receptor. Thus, CXCR4 expression of the tumor may predict response to radioiodine treatment. MATERIALS AND METHODS: Retrospective review of seventy-four PTC patients, treated with total/near-total thyroidectomy and radioiodine treatment at King Chulalongkorn Memorial Hospital from January 2007 to 2013, were classified as non-radioiodine-refractory (non-RAIR) or RAIR treatment response. All histopathologic diagnoses were reviewed and paraffin blocks were retrieved for CXCR4 immunostaining, determined by automated digital imaging analysis for intensity and extension. The scores were compared between primary tumour and adjacent normal thyroid tissue as well as between the tissue of non-RAIR and that of RAIR. Factors determining type of RAI response were analyzed. RESULTS: CXCR4 immunostaining scores of PTC is significantly higher than normal thyroid [2.03 (0.52) and 1.48 (0.75)] [mean (SD)] (P = 0.0001). CXCR4 immunostaining scores in RAIR are potentially higher than non-RAIR [1.95 (0.54) and 2.13 (0.47) (P = 0.149)]. Odds ratio of CXCR4 immunostaining score for predicting RAIR treatment is 1.99 (P = 0.150). CXCR4 immunostaining scores positively associate with tumor size (R = 0.298, P = 0.01); whereas no significant association with other clinicopathologic factors. CONCLUSION: Our data support the notion that CXCR4 are significantly expressed in PTC tumor over normal thyroid tissues. However, there is no clinical association with radioiodine treatment response.

Effects of vitamin D and calcium supplementation on bone mineral density among Thai youth using daily HIV pre-exposure prophylaxis.

INTRODUCTION: Tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) is used for HIV pre-exposure prophylaxis (PrEP). TDF may affect bone mineral density (BMD), particularly in youth who are at a stage of peak bone mass accrual. The objective of this study was to evaluate the effect of vitamin D and calcium supplementation on BMD among Thai youth receiving daily oral PrEP. METHODS: This open-label randomized trial was conducted in male youth aged between 15 and 24 years. Participants were randomized to Arm A who received once-daily TDF/FTC plus vitamin D3 and calcium supplementation with meals twice daily (400 units of vitamin D3 and 1200 mg of elemental calcium/day) or Arm B who received once-daily TDF/FTC only. PrEP users were defined as taking at least two tablets/week (tenofovir-diphosphate level of >350 fmol/punch). Adherence to vitamin D/calcium supplementation was defined as self-reported adherence of >50%. Lumbar spine (L2-L4) BMD (LSBMD) was evaluated by dual-energy X-ray absorptiometry scan zero and six months after PrEP initiation. RESULTS: From March 2019 to March 2020, 100 youth were enrolled. Baseline characteristics between the two arms were similar. Median (IQR) age was 18 (17 to 20) years. At entry, median (IQR) LSBMD z-score was -0.8 (-1.5 to -0.3), 17% had low LSBMD (Z-score < -2). The median amount of calcium intake from nutritional three-day recall was 167 (IQR 94 to 272) mg/day, 39% of participants had vitamin D deficiency, defined as 25(OH)D levels <20 IU/mL. At six months, 79 participants were evaluated. Of these, 42 (52%) were PrEP takers and 25 of 38 (66%) of arm A participants had good adherence to vitamin D/calcium supplementation. Significantly higher proportions of youth in arm A compared to arm B had >3% increase in LSBMD at month 6 compared to baseline (67.6% vs. 42.9% respectively; p = 0.03). There were significantly higher increases in LSBMD among youth with vitamin D deficiency who were supplemented; arm A + 0.05 (0 to 0.05) compared to arm B + 0.03 (-0.1 to 0.03), p = 0.04. CONCLUSIONS: Increases in LSBMD over six months among youth using PrEP who received vitamin D/calcium supplementation was greater than those not supplemented. Long-term follow-up should be considered to explore long-term outcomes.

Early prediction of donepezil cognitive response in Alzheimer's disease by brain perfusion single photon emission tomography.

Currently, there is no effective means to evaluate donepezil response. We evaluated brain perfusion change at 4 h after donepezil administration (4 h DNPZ) to predict cognitive responses after 6 months of medication. CERAD neuropsychological assessment battery was used to define cognitive response at 6 months. We compared 4 h DNPZ to baseline single photon emission tomography (SPECT) by statistical parametric mapping to identify perfusion changes in responders (N = 16) and non-responders (N = 7). In responders, there were significant relatively increase in perfusion in left parietal lobe (BA39, 7, 1), right superior frontal gyrus (BA6) and right middle occipital gyrus (BA39). In the non-responders, perfusion was relatively increase in the left parietal lobe (BA39) only. In an explorative analysis, we found a significant correlation between perfusion changes in right BA6 and CERAD score changes at 6 months. Different SPECT perfusion changes at 4 h after donepezil administration were demonstrated in the group of responders and non-responders with potential correlation with CERAD score change. Thus, 4 h DNPZ brain perfusion SPECT can be used to predict donepezil response at 6 months.

Finding the best effective way of treatment for rapid I-131 turnover Graves' disease patients: A randomized clinical trial.

BACKGROUND: Rapid I-131 turnover Graves' disease patients have low cure rate. We aimed to compare cure percentage at 12 months among 3 treatment doses of I-131 with or without lithium carbonate (LiCO3) in rapid turnover Graves' disease patients. METHODS: Sixty Graves' disease patients referred for radioactive iodine treatment were randomised into three arms of treatment: Group A, 3.7 MBq I-131/g thyroid plus 600 mg/day LiCO3, Group B, 5.55 MBq I-131/g plus 600 mg/day LiCO3, and Group C, 7.4 MBq I-131/g without LiCO3. Data were collected at baseline, 3, 6, 9, and 12 months. The primary endpoint were cure rates (percentage of euthyroid or hypothyroid) at 12 months. Pairwise comparisons were made across 3 groups using an equality of proportions test. The secondary endpoint, the odds of cure over the total follow-up for group B and C versus group A, was analyzed using generalized estimating equation (GEE). Side effects of I-131 and LiCO3 treatment were evaluated at 1 to 2 weeks after treatment. RESULTS: The cure rate at 12 months was 45% (9/20) for group A, 60% (12/20) for group B and 80% (16/20) for group C. The mean difference in proportion cured at 12 months between group C and group A was 35 (7.0 to 66.8)%; P-value = .02. There was a statistically significant difference between cure rates over all follow-up of group C and A after adjustment for sex (adjusted OR = 3.09; 95%CI = 1.32-7.20; P-value = .009), but no significant difference was found between group B and A or C and B in the primary and/or secondary efficacy endpoints. Side effects from the treatment were found in 12% (7/60); 2 in group A, 4 in group B, and 1 in group C. Four of these were likely due to LiCO3 side effects. CONCLUSIONS: Treatment of rapid turnover Graves' disease patients with high dose I-131 (7.4 MBq/g) provides significantly higher cure rates at 12 months, and 3 times odds of cure than 3.7 MBq/g I-131 plus LiCO3 with lesser side effects. We thus recommend 7.4 MBq I-131/g for treatment in these patients.

Impact of injection time on migration of SPECT seizure onset in temporal lobe epilepsy.

In this work, we investigated an impact of injection time on migration of seizure-onset in ictal/interictal single photon emission computed tomography (SPECT) study for patients with temporal lobe epilepsy. We selected 33 patients with refractory temporal lobe epilepsy who underwent ictal/interictal SPECT studies and had preoperative intracranial EEG result or surgical resection which was used as reference for seizure location. We divided all patients into two groups, which are the fast and the delayed groups; the delayed group comprised patients with injection time more than a cutoff time and vice versa. Using the subtraction ictal-interictal SPECT co-registered with SPECT (SISCOS) with varied Z-threshold (1.0, 1.5, 2.0 and 2.5), a method similar to subtraction ictal SPECT co-registered to magnetic resonance imaging (MRI) (SISCOM), a seizure-onset region in the SISCOS image was localized at the region with maximum sum of Z-scores. For each pair of cutoff time and Z-threshold, we determined the migratory proportion which was defined as the proportion of patients whose seizure-onset location based on SISCOS image was discordant with the reference. At cutoff time of 32-35 seconds and the Z-threshold of 2.0, the migratory proportion values were 7/26 (26.9%) and 5/7 (71.4%) in the fast and the delayed groups, respectively. At the same range of cutoff time with the Z-threshold of 2.5, the migratory proportion was 8/26 (30.8%) in the fast group while the proportion was 5/7 (71.4%) in the delayed group. Using Fisher's exact test, the migratory proportion values at the Z-threshold of 2.0 and 2.5 were significantly different between the fast and the delayed groups (p = 0.0709 and 0.0838, respectively), suggesting that patients with temporal lobe epilepsy who undergo an ictal/interictal SPECT study with injection time longer than 35 seconds tend to have seizure-onset zone migration in the SISCOS analysis with the traditionally-used Z-threshold of 2.0.

PSMA expression by microvasculature of thyroid tumors - Potential implications for PSMA theranostics.

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer epithelium, making it a promising target for molecular imaging and therapy. Recently, several studies found unexpected PSMA radiotracer uptake by thyroid tumors, including radioiodine-refractory (RAIR) cancers. PSMA expression was reported in tumor-associated endothelium of various malignancies, however it has not been systematically addressed in thyroid tumors. We found that PSMA was frequently expressed in microvessels of thyroid tumors (120/267), but not in benign thyroid tissue. PSMA expression in neovasculature was highly irregular ranging from 19% in benign tumors to over 50% in thyroid cancer. Such heterogeneity was not directly attributed to endothelial cell proliferation as confirmed by immunostaining with proliferation-associated endothelial marker CD105. PSMA expression was associated with tumor size (p = 0.02) and vascular invasion in follicular carcinoma (p = 0.03), but not with other baseline histological, and clinical parameters. Significant translational implication is that RAIR tumors and high-grade cancers maintain high level of PSMA expression, and can be targeted by PSMA ligand radiopharmaceuticals. Our study predicts several pitfalls potentially associated with PSMA imaging of the thyroid, such as low expression in oncocytic tumors, absence of organ specificity, and PSMA-positivity in dendritic cells of chronic thyroiditis, which is described for the first time.

Joint reconstruction of Ictal/inter-ictal SPECT data for improved epileptic foci localization.

PURPOSE: To improve the performance for localizing epileptic foci, we have developed a joint ictal/inter-ictal SPECT reconstruction method in which ictal and inter-ictal SPECT projections are simultaneously reconstructed to obtain the differential image. METHODS: We have developed a SPECT reconstruction method that jointly reconstructs ictal and inter-ictal SPECT projection data. We performed both phantom and patient studies to evaluate the performance of our joint method for epileptic foci localization as compared with the conventional subtraction method in which the differential image is obtained by subtracting the inter-ictal image from the co-registered ictal image. Two low-noise SPECT projection datasets were acquired using 99m Tc and a Hoffman head phantom at two different positions and orientations. At one of the two phantom locations, a low-noise dataset was also acquired using a 99m Tc-filled 3.3-cm sphere with a cold attenuation background identical to the Hoffman phantom. These three datasets were combined and scaled to mimic low-noise clinical ictal (three different lesion-to-background contrast levels: 1.25, 1.55, and 1.70) and inter-ictal scans. For each low-noise dataset, 25 noise realizations were generated by adding Poisson noise to the projections. The mean and standard deviation (SD) of lesion contrast in the differential images were computed using both the conventional subtraction and our joint methods. We also applied both methods to the 35 epileptic patient datasets. Each differential image was presented to two nuclear medicine physicians to localize a lesion and specify a confidence level. The readers' data were analyzed to obtain the localized-response receiver operating characteristic (LROC) curves for both the subtraction and joint methods. RESULTS: For the phantom study, the difference between the mean lesion contrast in the differential images obtained using the conventional subtraction versus our joint method decreases as the iteration number increases. Compared with the conventional subtraction approach, the SD reduction of lesion contrast at the 10th iteration using our joint method ranges from 54.7% to 68.2% (P < 0.0005), and 33.8% to 47.9% (P < 0.05) for 2 and 4 million total inter-ictal counts, respectively. In the patient study, our joint method increases the area under LROC from 0.24 to 0.34 and from 0.15 to 0.20 for the first and second reader, respectively. We have demonstrated improved performance of our method as compared to the standard subtraction method currently used in clinical practice. CONCLUSION: The proposed joint ictal/inter-ictal reconstruction method yields better performance for epileptic foci localization than the conventional subtraction method.