Performance of a deep learning enhancement method applied to PET images acquired with a reduced acquisition time.

BACKGROUND: This study aims to evaluate the performance of a deep learning enhancement method in PET images reconstructed with a shorter acquisition time, and different reconstruction algorithms. The impact of the enhancement on clinical decisions was also assessed. MATERIAL AND METHODS: Thirty-seven subjects underwent clinical whole-body [18F]FDG PET/CT exams with an acquisition time of 1.5 min per bed position. PET images were reconstructed with the OSEM algorithm using 66% counts (imitating 1 min/bed acquisition time) and 100% counts (1.5 min/bed). Images reconstructed from 66% counts were subsequently enhanced using the SubtlePET™ (SP) deep-learning-based software, (Subtle Medical, USA) - with two different software versions (SP1 and SP2). Additionally, images obtained with 66% counts were reconstructed with QClear™ (GE, USA) algorithm and enhanced with SP2. Volumes of interest (VOI) of the lesions and reference VOIs in the liver, brain, bladder, and mediastinum were drawn on OSEM images and copied on SP images. Quantitative SUVmax values per VOI of OSEM or QClear™ and AI-enhanced 'shortened' acquisitions were compared. RESULTS: Two hundred and fifty-two VOIs were identified (37 for each reference region, and 104 for the lesions) for OSEM, SP1, SP2, and QClear™ images AI-enhanced with SP2. SUVmax values on SP1 images were lower than standard OSEM, but on SP2 differences were smaller (average difference for SP1 11.6%, for SP2 -4.5%). For images reconstructed with QClear™, SUVmax values were higher (average +8.9%, median 6.1%, SD 18.9%). For small lesions with SUVmax values range 2.0 to 4.0 decrease of measured SUVmax was much less significant with SP2 (for liver average -6.5%, median -5.6% for lesions average -5.6%, median - 6.0, SD 5.2%) and showed the best correlation with original OSEM. While no artifacts and good general diagnostic confidence were found in AI-enhanced images, SP1, the images were not equal to the original OSEM - some lesions were hard to spot. SP2 produced images with almost the same quality as the original 1.5 min/bed OSEM reconstruction. CONCLUSIONS: The studied deep learning enhancement method can be used to accelerate PET acquisitions without compromising quantitative SUVmax values. AI-based algorithms can enhance the image quality of accelerated PET acquisitions, enabling the dose reduction to the patients and improving the cost-effectiveness of PET/CT imaging.

Modifying impact of RET gene haplotypes on medullary thyroid carcinoma clinical course.

The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which suggests the involvement of additional modulators of the disease. However, genetic factors responsible for this heterogeneity of the MTC clinical course still remain unknown. The aim of this study was to determine if polymorphic variants or specific haplotypes of the RET gene may modify the MTC clinical course. We genotyped the following loci: c.73+9277T>C, c.135G>A, c.1296A>G, c.2071G>A, c.2307T>C, c.2508C>T and c.2712C>G in 142 MTC patients and controls. We demonstrated considerable differences in the genotypes distribution within c.73+9277T>C, c.135G>A and c.2307T>C loci Our results show that the c.73+9277T variant associated with a decreased activity of the MCS+9.7 RET enhancer is rare in hereditary MTC patients with primary hyperparathyroidism, and thus, may influence the MTC clinical picture. The decreased activity of the RET promoter enhancer reduces RET expression level and may counterbalance the activating mutation in this gene. Frequent co-occurrence of the c.73+9277T allele with p.E768D, p.Y791F, p.V804M or p.R844Q RET mutations may be associated with their attenuation and milder clinical picture of the disease. Haplotypes analysis showed that C-G-A-G-T-(C)-C (c.73+9277T>C - c.135G>A - c.1296A>G - c.2071G>A - c.2307T>G - (c.2508C>T) - c.2712C>G) alleles combination predisposes to pheochromocytomas and primary hyperparathyroidism. We consider that RET haplotypes defining may become an auxiliary diagnostic tool in MTC patients.

Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt.

The role of autoimmunization in the pathogenesis of pituitary disorders is poorly understood. The presence of pituitary autoantibodies (APA) has been detected in various pituitary disorders. Their role, however, remains elusive. Childhood-onset combined pituitary hormone deficiency (CPHD) may be caused by environmental or genetic factors. In some of patients, causes of the disease remain unclear and contributions of autoimmune processes have been postulated. The aim of this study was to identify the microsomes-derived pituitary antigens (MPA) as potential immunogenic autoantigens in patients with hypopituitarism, therefore 62 CPHD patients, 100 healthy controls and five autoimmune polyglandular syndrome type II (APS II) patients were included in the study. The clinical evaluation included hormonal tests and magnetic resonance imaging of the pituitary. The sources of MPA were pituitary glands taken from autopsies. Isolated MPA were then separated on SDS-PAGE gel and incubated with sera obtained from patients and controls. Microsomal APA were detected using Western blot and radioimmunological method. In all CPHD and APS II patients and in 9 % individuals from control group marked immunoreactivity was detected against MPA. Antibodies showed high affinity to 67, 60, 50 and 36 kDa MPAs. Since the identified autoantigens were of unknown nature, an in silico exploration of UniProt database was applied and indicated their possible relationship with chaperones, golgins and already known autoantigens like GAD67. Reactivity against MPA indicates that these proteins certainly play a role in the processes undergoing within pituitary of CPHD patients. The identification and further detailed studies on their role in the pathogenesis of CPHD should be continued.

Diagnosis, treatment, and prognosis in patients with liver metastases from follicular thyroid carcinoma (FTC).

Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer (TC) and accounts for approximately 10% of all TC cases. Liver metastases are a rare presentation in 0.5-1% of follicular thyroid cancers, usually occurring in the setting of widely disseminated FTC disease, and their presence is associated with poor prognosis. Until now, there have been only 30 cases of FTC liver metastases described in the literature. Herein, we review publications and describe diagnostic tools that may be used in the diagnosis and follow-up of FTC metastases to the liver, including biopsy and imaging techniques like US, CT, MRI, SPECT, PET, and radioiodine scintigraphy. We also present and discuss current methods of treatment, e.g. TSH suppressive therapy with levothyroxine, surgery, radiofrequency ablation (RFA), transarterial embolisation (TAE), liver transarterial chemoembolisation (TACE), chemotherapy with cisplatin and doxorubicin, treatment with Indium- 111-octreotide (or its analogues), and tyrosine kinase inhibitors (sorafenib, sunitinib). At the end we describe the course, results of diagnostics, and treatment in a patient with large multiple FTC metastases to the liver. (Endokrynol Pol 2016; 67 (3): 332-347).

The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population.

BACKGROUND: Differentiated thyroid carcinoma (DTC) originates from thyroid follicular epithelial cells and belongs to a group of slowly progressing tumors with a relatively good prognosis. However, recurrences and metastases are a serious problem in advanced stages. Furthermore, progression from a well differentiated thyroid carcinoma to an aggressive anaplastic one is possible. The majority of differentiated thyroid carcinomas are sporadic but a few alleles increasing the cancer risk are known. One of them is the c.470 T > C (p.I157T, rs17879961) missense substitution in the CHEK2 gene. AIM OF THE STUDY: The aim of this study was to investigate whether this specific CHEK2 alteration, c.470 T > C, predisposes the Great Poland (Wielkopolska) population to thyroid cancer. METHODS: 602 differentiated thyroid carcinoma patients and 829 controls randomly selected from population were genotyped for the presence of the c.470C allele using pyrosequencing. Hardy-Weinberg Equilibrium (HWE) was tested for both groups by chi-square distribution and Fisher's exact test. The odds ratios (ORs), 95% confidence intervals (CIs), and p-values were calculated using the R software. RESULTS: The results of genotyping showed the presence of the c.470C allele in 51 patients with a frequency of 4.49%, while in a controls in 42 patients with a frequency of 2.53%. We demonstrated that in the Great Poland population the c.470C CHEK2 variant increases the risk of developing differentiated thyroid cancer almost twice (OR = 1.81, p = 0.004). The risk of papillary thyroid carcinoma in female patients homozygous for the c.470C allele was shown to increase almost 13-fold (OR = 12.81, p = 0.019). CONCLUSIONS: Identification of c.470C CHEK2 gene variant ought to be taken into account by healthcare policymakers. Future well-designed and larger population studies are of great value in confirming these findings. Moreover, a combination of genetic factors together with environmental exposures should also be considered.

Emotional functions in transsexuals after the first step in physical transformation.

Transsexuals have to face multiple medical, social and bureaucratic problems. These problems are not only encountered before the transformation, but also during and after medical procedures. In the search for improvement of transsexual individuals' quality of life during therapy, it seems desirable to supplement hormonal treatments with psychological explorations. This study was conducted with the aim of defining emotional conditions and included 28 transsexual female-to-male (F/M) patients and two gender-divided control groups (males and females) of similar age. The following psychometric scales were used: CECS (Courtauld Emotional Control Scale constructed by M. Watson and S. Greer in the Polish Adaptation by Z. Juczynski), ISCL (the Polish Adaptation of the State-Trait Anxiety Inventory for Adults by T. Sosnowski), and GSES (the Polish Adaptation of the R. Schwarzer, M. Jerusalem Generalized Self-Efficacy Scaleby Z. Juczynski and K. Wrzesniewski). Transsexual F/M patients appeared very similar to males in the male control group in terms of their subjective selfefficacy and state-trait anxiety, while their subjective belief of anxiety and fear control was more comparable to that of the female controls. It was also found to be statistically significantly lower than in the male controls.

CCND1 gene polymorphic variants in patients with differentiated thyroid carcinoma.

Alterations in the CCND1 gene affect the cell cycle and are frequently observed in a variety of cancers. While the most frequent mutations that occur in thyroid tumor tissue have been characterized, the genetic factors that predispose individuals to differentiated thyroid cancer (DTC) remain to be elucidated. The present study examined whether the CCND1 c.723G>A (rs9344; p.Pro241=) and c.669C>T (rs3862792; p.Phe223=) variants have an impact on DTC susceptibility. A cohort consisting of 652 patients diagnosed with DTC were analyzed and comapred with a reference group of 799 subjects from the general population. Pyrosequencing was used as the genotyping technique. In order to determine the statistical significance of differences observed in the genotypic and allelic frequencies between the compared groups, GraphPad Prism 4 was used. At the rs9344 locus in the DTC patients, a higher frequency of allele A [P=0.032; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.014-1.361] and the AA homozygous genotype (P=0.028; OR, 1.41; 95% CI, 1.059-1.989) was observed compared with the control population group. The differences were stronger for papillary carcinomas (OR 1.45; 95% CI, 1.059-1.989), but were not significant in follicular tumors. No statistically significant differences were noted in the frequency of genotypes or alleles at the rs3862792 locus in the examined groups. The present findings indicate that the c.723A variant of the CCDN1 gene may be a susceptibility low penetrance allele in the development of papillary thyroid cancer in the population studied, however it does not impact on multifocality, metastatic ability or age at diagnosis. A cumulative effect of the analyzed CCND1 gene variants was also excluded.

[Significance of visual evoked potentials (VEP) in the diagnosis of Parkinson disease]. / Znaczenie wzrokowych potencjalów wywolanych (VEP) w diagnostyce choroby Parkinsona.

The aim of the study was to check whether VEP in Parkinson disease are pathological and if there is a relationship between VEP studies and severity, duration of the disease. The authors recruited 54 patient with idiopathic Parkinson disease with significant differences in laterality of bradykinesia, rigidity and tremor. The examined group consisted of 25 males and 29 females, aged from 34 to 82 years; mean age 70.47; the disease duration--from 3 month to 20 years; mean duration 7.76. The asymmetry of extra-pyramidal symptoms, severity of disease with UPDRS and activities of daily living with Schwabach and England were evaluated. Age, disease duration, treatment duration, current dose and side effects of levodopa were taken into account. Neurological examination and VEP were performed before the morning dose of levodopa U-test and Spearman correlation were used for statistical analysis. The VEP latencies were found in 11 patients (15.94%). Mean VEP latency for the right eye in this group was 116.83 (range: 122.3-111.0) and 120.45 (range: 161.5-111.0) for the left. In the group of patients with normal VEP the results were respectively 99.91 and 100.39. There were no significant correlations between the VEP and the asymmetry of neurological symptoms, disease severity and duration, treatment duration, the dose and side effects of Levodopa. There was a significant relationship between VEP latency and patients age and activities of daily living.

[Depression in Parkinson disease: own experience]. / Depresja w chorobie Parkinsona--wlasne doswiadczenia.

The aim of the study was to evaluate the frequency of depression in patients with Parkinson's disease. The authors recruited 85 patients with idiopathic Parkinson's disease, 42 males and 43 females aged 34-82 years (mean age 68.7). Age at onset ranged 24-79 (mean 60.9 years). Disease duration ranged from 3 month to 20 years (mean 7.86 years). In 62 patients (72.94%) mixed type of the disease was diagnosed, in 14 (16.47%) tremor and in 9 (10.59%) rigidity predominated. UPDRS was used to evaluate the severity of the disease (results ranged 28-90, mean 51.4). Activity of daily living was estimated according to Schwab and England Scale (range 40-90, mean 68.1). Depression was evaluated with Hamilton, Beck and Montgomery-Asberg scales. The results were analysed with Spearman correlation. Depression was diagnosed in 53 (62.35%) patients [in 7 (8.24%) light; in 14 (16.47%) middle; in 19 (22.35%) heavy; in 13 (15.29%) very heavy]. The results acquired with all three scales were not statistically different. There were significant positive correlations between depression and female sex, severity of the disease, dyskinesia as side effect of.