Volume and Permeability of White Matter Hyperintensity on Cognition: A DCE Imaging Study of an Older Cohort With and Without Cognitive Impairment.

BACKGROUND: The impact of blood-brain barrier (BBB) leakage on white matter hyperintensity (WMH) subtypes (location) and its association with clinical factors and cognition remains unclear. PURPOSE: To investigate the relationship between WMH volume, permeability, clinical factors, and cognition in older individuals across the cognitive spectrum. STUDY TYPE: Prospective, cross-sectional. SUBJECTS: A total of 193 older adults with/without cognitive impairment; 128 females; mean age 70.1 years (standard deviation 6.8). FIELD STRENGTH/SEQUENCE: 3 T, GE Dynamic contrast-enhanced, three-dimensional (3D) Magnetization-prepared rapid gradient-echo (MPRAGE T1WI), 3D fluid-attenuated inversion recovery (FLAIR). ASSESSMENT: Periventricular WMH (PWMH), deep WMH (DWMH), and normal-appearing white matter (NAWM) were segmented using FMRIB automatic segmentation tool algorithms on 3D FLAIR. Hippocampal volume and cortex volume were segmented on 3D T1WI. BBB permeability (Ktrans) and blood plasma volume (Vp) were determined using the Patlak model. Vascular risk factors and cognition were assessed. STATISTICAL TESTS: Univariate and multivariate analyses were performed to identify factors associated with WMH permeability. Logistic regression analysis assessed the association between WMH imaging features and cognition, adjusting for age, sex, apolipoprotein E4 status, education, and brain volumes. A P-value <0.05 was considered significant. RESULTS: PWMH exhibited higher Ktrans (0.598 ± 0.509 × 10-3 minute-1) compared to DWMH (0.496 ± 0.478 × 10-3 minute-1) and NAWM (0.476 ± 0.398 × 10-3 minute-1). Smaller PWMH volume and cardiovascular disease (CVD) history were significantly associated with higher Ktrans in PWMH. In DWMH, higher Ktrans were associated with CVD history and cortical volume. In NAWM, it was linked to CVD history and dyslipidemia. Larger PWMH volume (odds ratio [OR] 1.106, confidence interval [CI]: 1.021-1.197) and smaller hippocampal volume (OR 0.069; CI: 0.019-0.253) were independently linked to worse global cognition after covariate adjustment. DATA CONCLUSION: Elevated BBB leakage in PWMH was associated with lower PWMH volume and prior CVD history. Notably, PWMH volume, rather than permeability, was correlated with cognitive decline, suggesting that BBB leakage in WMH may be a consequence of CVD rather than indicate disease progression. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Effect of Rowachol on the Gallbladder Dysmotility Disorder Based on Gallbladder Ejection Fraction.

Background and Objectives: Although laparoscopic cholecystectomy is the preferred treatment method in patients who experience typical biliary pain with or without gallstones, medical treatment has not been extensively studied. Rowachol is a potent choleretic agent, comprising six cyclic monoterpenes. This study aimed to investigate the clinical improvement and changes in gallbladder ejection fraction (GBEF) by Rowachol treatment in patients with typical biliary pain. Materials and Methods: We retrospectively reviewed 138 patients with typical biliary pain who underwent cholescintigraphy from July 2016 to April 2022. We included patients who received Rowachol for more than 2 months and underwent follow-up GBEF measurements. Finally, we analyzed pre- and post-treatment symptoms and GBEF. GBEF was calculated using the fatty meal-stimulated cholescintigraphy. Results: This retrospective observational study included 31 patients; their median age was 46.0 (range, 26.0-72.7) years, and 22 (71.0%) were female. Overall, 9 (29.0%) patients had gallbladder stones or sludges (maximum size: 2 mm) on initial transabdominal ultrasonography. During a median follow-up of 23.3 months, the symptoms of 21 (67.7%) patients were resolved after a median Rowachol treatment of 10.0 months. The mean GBEF was significantly improved after Rowachol treatment (initial cholescintigraphy: 42.6% ± 16.2%; follow-up cholescintigraphy: 53.0% ± 18.1%, p = 0.012). In patients with a GBEF ≤35% (n = 9), Rowachol significantly increased the GBEF from 21.3% ± 8.3% to 49.1% ± 20.7% (p = 0.008). Conclusions: Rowachol may have beneficial medical effects that can improve gallbladder dysfunction and treatment response.

Correlation between salivary gland ultrasonography and scintigraphy in primary Sjögren's syndrome.

OBJECTIVE: To compare findings on salivary gland ultrasonography (SGUS) and salivary gland scintigraphy (SGS) in patients with primary SS (pSS). METHODS: The study cohort included patients newly diagnosed with pSS who underwent SGUS and SGS at the same time at our tertiary care hospital. Baseline demographics, laboratory data, clinical data and SGUS and SGS findings were collected. An SGUS cut-off score ≥14 defined positive SGUS findings and was used to classify patients in SGUS+ and SGUS- groups. SGS findings were quantified by the parotid:submandibular uptake ratio (PU:SU) and percentage parotid/submandibular excretion (%PE/%SE). The correlation between SGUS and SGS findings was evaluated. RESULTS: For analysis, 18 patients with SGUS+ findings and 18 with SGUS- findings were recruited, for a total study cohort of 36 patients. There were no between-group differences in baseline demographics and clinical and laboratory data. The PU, %PE, SU and %SE were significantly lower in the SGUS+vs SGUS- group. The SGUS score for the parotid gland was negatively correlated to the PU (r = -0.36, P = 0.03) and %PE (r = -0.35, P = 0.04). The SGUS score of the submandibular gland was negatively correlated to the SU (r = -0.42, P = 0.01) and %SE (r = -0.39, P = 0.02). CONCLUSIONS: Patients with a higher SGUS score had lower salivary gland function. The SGUS score showed a significant correlation with PU, %PE, SU and %SE. These findings are indicative of a possible predictive role of SGUS to diagnose salivary gland dysfunction.

Semiquantitative analysis of sacroiliac joint to sacrum ratio of bone scintigraphy to predict spinal progression in early axial spondyloarthritis: a pilot study.

OBJECTIVES: To investigate whether bone scintigraphy with semiquantitative analysis in patients with early axial spondyloarthritis (axSpA) has prognostic value for predicting spinal structural progression of these patients after 2 years. METHODS: The records of 53 patients with early axSpA who underwent baseline bone scintigraphy were reviewed retrospectively. The sacroiliac joint to sacrum (SIS) ratio of bone scintigraphy was measured for semiquantitative analysis, and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and syndesmophyte growth were calculated at baseline and after 2 years. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off for the SIS ratio of bone scintigraphy. To identify factors associated with significant spinal structural progression, univariate and multivariate logistic regression analyses were performed. Significant progression of spinal structural damage over 2 years was defined as an increase of mSASSS of at least 2 units for 2 years or new syndesmophyte growth/bridging of pre-existing syndesmophytes. RESULTS: Multivariate regression analysis revealed current smoking status (p=0.010), and high SIS ratio of bone scintigraphy (p=0.016) as independent predictors for worsening mSASSS by at least 2 units over 2 years. For new syndesmophyte growth/bridging of pre-existing syndesmophytes over 2 years, current smoking (p=0.013), high SIS ratio of bone scintigraphy (p=0.025), and pre-existing syndesmophyte (p=0.036) were independent predictors. CONCLUSIONS: Semiquantitative analysis of bone scintigraphy (high SIS ratio) in patients with early axSpA may be useful for identifying patients at high risk for spinal structural progression after 2 years.

GANGLION CELL-INNER PLEXIFORM LAYER THICKNESS IN EYES WITH NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION OF DIFFERENT DRUSEN SUBTYPES.

PURPOSE: We sought to investigate the ganglion cell-inner plexiform layer (GCIPL) thickness in eyes with nonexudative age-related macular degeneration. METHODS: We classified eyes into four categories-pachydrusen, soft drusen, subretinal drusenoid deposit (SDD), and soft drusen with SDD-and compared the baseline mean macular GCIPL thickness according to the Early Treatment Diabetic Retinopathy Study grid and its change between groups. RESULTS: We classified 53, 29, 36, and 34 eyes into the four categories, respectively. The mean GCIPL thickness values in the 3-mm area were 82.61 ± 9.54 µm for the pachydrusen group, 79.11 ± 10.26 µm for the soft drusen group, 77.72 ± 6.04 µm for the SDD group, and 71.63 ± 8.69 µm for the soft drusen with SDD group (P < 0.001). The soft drusen with the SDD group showed a greater change in GCIPL thickness (-2.50 ± 0.29 µm/year) in the 3-mm area as compared with the pachydrusen group (-0.18 ± 0.35 µm/year), soft drusen group (-0.55 ± 0.36 µm/year), and SDD group (-0.55 ± 0.37) (all P < 0.001). CONCLUSION: The GCIPL thickness varied according to the type of nonexudative age-related macular degeneration. The thinner baseline GCIPL and its greater change in eyes with soft drusen with SDD may suggest that these eyes are experiencing more prominent neuroretinal degeneration in the central 3-mm area than those in the other groups.

Absent Bell's phenomenon in patients with thyroid eye disease.

BACKGROUND: To investigate the incidence of absent Bell's phenomenon (BP) and the relationship between absent BP and inferior rectus muscle hypertrophy and other clinical features in patients with thyroid eye disease (TED). METHODS: A total of 104 patients who were first diagnosed with TED between January and December 2014 were included. Inferior rectus muscle area and associations with clinical features of TED and thyroid function test including thyroid specific antibodies were compared between patients with TED with and without BP. The volume of the inferior rectus muscle was calculated by adding up all the cross-sectional areas measured on sagittal CT images. RESULTS: Among the 104 patients, 14 had absent BP (13.5%), 12 with bilateral and two with unilateral. There was no significant difference in thyroid function test, presence of TSIs, exophthalmos, or volume of inferior rectus muscle measured in CT scans (P > 0.05). Incidence of diplopia, elevation limitation, and upper eyelid retraction were risk factors of absent BP in TED patients (by logistic regression analysis, P < 0.05). CONCLUSIONS: Inferior rectus muscle hypertrophy was not the cause of absent BP in TED patients. Fibrosis and tightening of the inferior rectus muscle, lower eyelid, and surrounding orbital tissues, rather than inferior rectus muscle hypertrophy, might be related to absent BP in TED patients.

Factors for good near and distance visual outcomes of multifocal intraocular lens with inferior segmental near add.

PURPOSE: This study was conducted to investigate factors related to postoperative good near and distance visual outcomes in the Lentis Mplus LS-313 MF20 (Oculentis Gmbh, Berlin, Germany) intraocular lens (IOL)-implanted eye. METHODS: A retrospective cross-sectional study analyzed a total of 198 eyes of 198 patients. Patients with 20/20-or-more uncorrected distance visual acuity (UDVA, 5 m) and J2-or-more uncorrected near visual acuity (UNVA, 40 cm) were distributed into the good visual outcome (GVO) group (n = 96), and the remaining patients were distributed into the moderate visual outcome (MVO) group (n = 102). Differences between the two groups were compared for patient age, preoperative measurements (kappa distance, kappa angle, and pupil size), and postoperative measurements (residual sphere, cylinder, and spherical equivalent) to explore factors related to good visual outcomes after IOL implantation. RESULTS: The average age of the GVO group (56.2 years) was significantly lower than that of the MVO group (58.6 years), and the average kappa distance of the former was significantly smaller than that of the latter. However, there were no significant differences between the two groups in kappa angle and pupil size. Notably, multivariate binary regression analysis revealed that multiple factors including age, residual cylinder, and spherical equivalent were associated with good visual outcomes. Based on the receiver operating characteristic curve, cutoff values regarded as good visual outcome following cataract surgery were calculated to be - 0.38 CD in residual cylinder and - 0.32 D in residual spherical equivalent. CONCLUSIONS: Patients with implanted Lentis Mplus LS-313 MF20 IOL who are young, had small kappa distance, and had low levels of postoperative residual cylinder and spherical equivalent tended to exhibit good vision at both near and distance. These results imply that surgeons should minimize postoperative residual cylinder and spherical equivalent to provide good visual outcomes to patients with implanted Lentis Mplus LS-313 MF20 IOL.

FEATURES OF THE MACULAR AND PERIPAPILLARY CHOROID AND CHORIOCAPILLARIS IN EYES WITH NONEXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We investigated macular and peripapillary choroidal thickness (CT) and flow voids in the choriocapillaris in eyes with nonexudative age-related macular degeneration. METHODS: We retrospectively reviewed the medical records of patients with nonexudative age-related macular degeneration and classified their eyes into three categories: pachydrusen, drusen, and subretinal drusenoid deposit. Mean macular and peripapillary CT and choriocapillaris flow void area were compared among the three groups. RESULTS: The three groups included 29, 33, and 33 patients, respectively. The mean macular and peripapillary CT findings were 260.64 ± 75.85 µm and 134.47 ± 46.28 µm for the pachydrusen group; 163.63 ± 64.08 µm and 93.47 ± 39.07 µm for the drusen group; and 95.33 ± 28.87 µm and 56.06 ± 11.64 µm for the subretinal drusenoid deposit group (all, P < 0.001). Mean macular and peripapillary flow void area varied among the subretinal drusenoid deposit group (57.07 ± 6.16% and 55.38 ± 6.65%), drusen group (58.30 ± 6.98% and 49.11 ± 9.11%) and pachydrusen group (50.09 ± 5.77% and 45.47 ± 8.06%) (all P < 0.001). CONCLUSION: The peripapillary CT and flow voids in the choriocapillaris varied according to the features of drusen in nonexudative age-related macular degeneration eyes. Greater flow voids and thinner CT in eyes with subretinal drusenoid deposits may suggest that these eyes have diffuse choroidal abnormalities both in and outside the macula.

DJ-1 is involved in epigenetic control of sphingosine-1-phosphate receptor expression in vascular neointima formation.

DJ-1 and sphingosine-1-phosphate (S1P) receptors (S1PRs) are implicated in the control of physiology and pathophysiology of cardiovascular systems such as blood pressure, atherosclerosis, and restenosis. Here, we investigated whether DJ-1 with antioxidant function participates in the regulation of S1PR1 and S1PR2 expression in vascular smooth muscle cells (VSMCs) and whether this response is related to vascular neointima formation. In vitro studies used cellular migration assay, western blot, reverse transcriptase and real-time PCR analysis, and immunocytochemistry. In vivo studies were performed using the carotid artery ligation model together with immunohistochemistry in DJ-1 knockout (DJKO) and corresponding wild-type (DJWT) mice. S1P stimulated migration of VSMCs from DJKO and DJWT mice. VSMC migration was suppressed by S1PR1 inhibitor but was elevated by S1PR2 inhibitor. Compared with DJWT mice, S1PR1 expression was higher in VSMCs and neointimal plaque from DJKO mice, but S1PR2 expression was lower. Overexpression of DJ-1 in DJKO VSMCs reduced S1PR1 expression and elevated S1PR2 expression. Compared with DJWT mice, histone deacetylase-1 recruitment and histone H3 acetylation at the S1PR1 promoter region were lower and higher, respectively, but this pattern was reversed at the S1PR2 promoter region in DJKO VSMCs. S1PR expressions and epigenetic changes at S1PR promoter regions in DJWT VSMCs treated with H2O2 showed similar patterns to those in DJKO VSMCs. Our findings suggest that DJ-1 may be involved in the regulation of S1PR1 and S1PR2 expression via H2O2-mediated histone modification in VSMCs. Consequently, this modification may affect S1P-induced VSMC migration and be related to vascular neointima formation.

Angiotensin II facilitates neointimal formation by increasing vascular smooth muscle cell migration: Involvement of APE/Ref-1-mediated overexpression of sphingosine-1-phosphate receptor 1.

Angiotensin II (Ang II) is implicated in the development of cardiovascular disorders including hypertension and atherosclerosis. However, the role of Ang II in the interaction between apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1) and sphingosine-1-phosphate (S1P) signals in relation to vascular disorders remains to be clarified. This study aimed to determine whether APE/Ref-1 plays a role in epigenetic regulation of the S1P receptor (S1PR) in response to Ang II in vascular smooth muscle cell (VSMC) migration and vascular neointima formation. Ang II augmented the expression of S1PR1 in aortic smooth muscle cells of Sprague Dawley rats (RASMCs), which was attenuated by Ang II receptor (AT) 1 inhibitors, antioxidants, and APE/Ref-1 knockdown with small interference RNA. Ang II stimulation produced H2O2, and exogenous H2O2 elevated S1PR1 expression in RASMCs. Moreover, Ang II caused translocation of cytoplasmic APE/Ref-1 into the nucleus in RASMCs. H3 histone acetylation and APE/Ref-1 binding at the S1PR1 promoter were increased in RASMCs treated with Ang II. In addition, Ang II induced migration in RASMCs, which was suppressed by AT1 and S1PR1 inhibitors. The expression of S1PR1, and colocalization of APE/Ref-1 and acetylated histone H3 in vascular neointima, were greater in Ang II-infused rats compared with a control group. These findings demonstrate that Ang II stimulates the epigenetic regulation of S1PR1 expression via H2O2-mediated APE/Ref-1 translocation, which may consequently be involved in Ang II-induced VSMC migration and vascular neointima formation. Therefore, APE/Ref-1-mediated overexpression of S1PR1 may be implicated in the vascular dysfunction evoked by Ang II.

Adjunctive Breast-Specific Gamma Imaging for Detecting Cancer in Women with Calcifications at Mammography.

BACKGROUND: Mammography detects calcium deposits sensitively, but the specificity for differentiating malignancy from benign calcifications is low. Thus, we investigated whether adjunctive breast-specific gamma imaging (BSGI) has incremental value for detecting cancer in women with suspicious calcifications detected by mammography, and compared BSGI with adjunctive ultrasonography (US). METHODS: The medical records of women without a personal history of breast cancer who underwent mammography for breast evaluation from 2009 to 2014 were reviewed retrospectively. Patients who had calcifications detected by mammography, with a result of Breast Imaging Reporting and Data System (BI-RADS) categories 3-5, underwent adjunctive US and BSGI and were included in this study. A total of 302 breast lesions in 266 women (mean age ± standard deviation 49 ± 9 years) were selected for this study. RESULTS: For detecting breast cancer using mammography plus BSGI, the sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve with 95% confidence intervals were 94% (91-96), 90% (86-93), 91% (87-94), 94% (90-96), and 0.92 (0.89-0.95), respectively. For mammography plus US, the respective values were 97% (94-98), 51% (46-57), 68% (63-73), 94% (90-96), and 0.74 (0.70-0.78). CONCLUSIONS: Adjunctive BSGI had higher specificity than adjunctive US without loss of sensitivity. This finding suggests that adjunctive BSGI may be a useful complementary initial imaging method to improve the detection of breast cancer in women who have calcifications with suspicious morphology at mammography.

Detection of skeletal muscle metastasis: torso FDG PET-CT versus contrast-enhanced chest or abdomen CT.

BACKGROUND: Skeletal muscle metastasis (SMM) in cancer patients has not been sufficiently evaluated regarding prevalence and proper method of detection. PURPOSE: To determine the prevalence of SMM and compare the diagnostic competencies for SMM of torso F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) and contrast-enhanced chest or abdomen CT. MATERIAL AND METHODS: We investigated 18,225 PET-CT studies of 6359 cancer patients performed from 2005 to 2012. The PET-CT studies describing potential SMM were retrieved and the corresponding medical records were reviewed. The gold standard for SMM was histopathologically-proven SMM or imaging study-based disease progression. The detectability of SMM was compared between PET-CT and contrast-enhanced CT. RESULTS: Twenty-six patients had 84 SMM lesions, representing a SMM prevalence of 0.41%. Lung cancer was the most common SMM-associated malignancy (54%) and the gluteal/pelvic girdle muscle was the most frequently involved SMM site (37%). All 84 SMM lesions were visualized on PET-CT (100%). Of these PET-CT positive 84 SMM lesions, 51 lesions were in the CT field of view (FOV) (61%), whereas 33 lesions were out of the CT FOV (39%). Among these 51 lesions, 17 lesions showed rim-enhancing nodules/masses (33%), eight lesions showed homogeneously enhancing nodules (16%), three lesions showed heterogeneously enhancing nodules (6%), and 23 SMM lesions (45%) were non-diagnostic by CT. All 51 SMM lesions within CT FOV were detected on PET-CT (100%), whereas only 28 were visualized on CT (54.9%), resulting in a significant difference (P < 0.005). On average, 2.6 more organs with concomitant metastases were found when SMM was revealed by PET-CT. CONCLUSION: The prevalence of SMM was as low as 0.41% in the current large cohort of cancer patients. Torso PET-CT was a more competent modality than contrast-enhanced CT in the detection of SMM.

Complementary role of semiquantitative analysis of breast-specific gamma imaging in the diagnosis of breast cancer.

OBJECTIVE: We investigated whether the interpretation of breast-specific gamma imaging (BSGI) with visual and semiquantitative analyses can improve the diagnosis of breast cancer. MATERIALS AND METHODS: The records of 114 women (mean age±SD, 49.6±9.8 years) who underwent BSGI, mammography, and ultrasound to evaluate a breast lesion or lesions were reviewed retrospectively. The breast lesions identified with BSGI were compared with those identified with mammography and ultrasound. BSGI was first interpreted visually, and then a semiquantitative analysis was performed. For the semiquantitative analysis, the uptake ratio for each breast lesion was calculated by dividing the tumor uptake by the contralateral normal breast uptake. RESULTS: Four of the 114 patients had two breast lesions, so a total of 118 breast lesions (42 malignant lesions and 76 benign lesions) were evaluated. A BSGI uptake ratio cutoff of 1.5, with values less than 1.5 indicating negative for cancer, as determined by receiver operating characteristic curve analysis of our data (area under curve, 0.874), was used for semi-quantitative analysis. The sensitivity and specificity of BSGI with visual analysis alone for assessing malignant breast lesions were 76.2% (32/42) and 81.6% (62/76), respectively. For BSGI with visual and semiquantitative analyses, the sensitivity and specificity were 76.2% (32/42) and 92.1% (70/76), respectively. The sensitivity and specificity for mammography were 57.1% (24/42) and 81.6% (62/76), respectively. For ultrasound, the respective values were 97.6% (41/42) and 61.8% (47/76). BSGI with visual and semiquantitative analyses had a significantly higher specificity than BSGI with visual analysis alone, mammography, and ultrasound (all, p<0.01). CONCLUSION: Semiquantitative analysis of BSGI with visual interpretation may be a useful complementary method for evaluating malignant breast lesions.

PET/MRI and Novel Targets for Breast Cancer.

Breast cancer, with its global prevalence and impact on women's health, necessitates effective early detection and accurate staging for optimal patient outcomes. Traditional imaging modalities such as mammography, ultrasound, and dynamic contrast-enhanced magnetic resonance imaging (MRI) play crucial roles in local-regional assessment, while bone scintigraphy and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) aid in evaluating distant metastasis. Despite the proven utility of 18F-FDG PET/CT in various cancers, its limitations in breast cancer, such as high false-negative rates for small and low-grade tumors, have driven exploration into novel targets for PET radiotracers, including estrogen receptor, human epidermal growth factor receptor-2, fibroblast activation protein, and hypoxia. The advent of PET/MRI, which combines metabolic PET information with high anatomical detail from MRI, has emerged as a promising tool for breast cancer diagnosis, staging, treatment response assessment, and restaging. Technical advancements including the integration of PET and MRI, considerations in patient preparation, and optimized imaging protocols contribute to the success of dedicated breast and whole-body PET/MRI. This comprehensive review offers the current technical aspects and clinical applications of PET/MRI for breast cancer. Additionally, novel targets in breast cancer for PET radiotracers beyond glucose metabolism are explored.

Artificial intelligence-based CT-free quantitative thyroid SPECT for thyrotoxicosis: study protocol of a multicentre, prospective, non-inferiority study.

INTRODUCTION: Technetium thyroid uptake (TcTU) measured by single-photon emission CT/CT (SPECT/CT) is an important diagnostic tool for the differential diagnosis of Graves' disease and destructive thyroiditis. Artificial intelligence (AI) may reduce CT-induced radiation exposure by substituting the role of CT in attenuation correction (AC) and thyroid segmentation, thus realising CT-free SPECT. This study aims to compare the diagnostic accuracy for the differential diagnosis of thyrotoxicosis between CT-free SPECT and SPECT/CT. METHODS AND ANALYSIS: The AI-based CT-free SPECT is a single-blind, multicentre, prospective, non-inferiority, clinical trial with a paired design conducted in the Republic of Korea. Eligible participants are adult (≥19 years old) thyrotoxicosis patients without a previous history of hyperthyroidism or hypothyroidism. Approximately 160 subjects will be screened for quantitative thyroid SPECT/CT using Tc-99m pertechnetate. CT-free thyroid SPECT will be realised using only SPECT data by the trained convolutional neural networks. TcTU will be calculated by SPECT/CT and CT-free SPECT in each subject. The primary endpoint is the accuracy of diagnosing Graves' disease using TcTU. The trial will continue until 152 completed datasets have been enrolled to assess whether the 95% (two-sided) lower confidence limit of the accuracy difference (CT-free SPECT accuracy-SPECT/CT accuracy) for Graves' disease is greater than -0.1. The secondary endpoints include the accuracy of diagnosing destructive thyroiditis and predicting the need for antithyroid drug prescription within 1 month of the SPECT/CT. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board of Seoul National University Bundang Hospital (IRB No. B-2304-824-301), Konkuk University Medical Center (IRB No. 2023-05-022-006) and Chonnam National University Hospital (IRB No. CNUH-2023-108). Findings will be disseminated as reports, presentations and peer-reviewed journal articles. TRIAL REGISTRATION NUMBER: KCT0008387, Clinical Research Information Service of the Republic of Korea (CRIS).

Gastric cancers with microsatellite instability exhibit high fluorodeoxyglucose uptake on positron emission tomography.

BACKGROUND: Gastric cancers exhibit various degrees of (18)F-fluorodeoxyglucose (FDG) uptakes on positron emission tomography/computed tomography (PET/CT) imaging. The aim of this study was to evaluate whether FDG uptake in gastric cancer varies according to the microsatellite instability (MSI) status. METHODS: Consecutive gastric cancer patients who underwent PET/CT imaging and MSI analysis were included in the study. The maximum standardized uptake value (SUVmax) of gastric cancer was assessed using PET/CT imaging. RESULTS: Of 131 gastric cancers, 16 exhibited a high incidence of MSI (MSI-H) and 3 exhibited a low incidence of MSI (MSI-L). In 29 subjects who showed no uptake on PET/CT imaging the gastric cancers were all microsatellite stable (MSS). Gastric cancers with MSI were related to age older than 60 years (p = 0.002), cancer volume larger than 10 cm(3) (p = 0.015), and the presence of FDG uptake on PET/CT imaging (p = 0.001). A higher SUVmax of gastric cancer was linked to the presence of MSI (p < 0.001). CONCLUSION: The presence of MSI is related to FDG uptake in gastric cancer. Care should be taken with MSS gastric cancers, because they show lower SUVmax on PET/CT imaging than MSI gastric cancers.

FDG PET/CT Maximum Tumor Dissemination to Predict Recurrence in Patients with Diffuse Large B-Cell Lymphoma.

Purpose: We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL).We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL). Methods: Patients who underwent FDG PET/CT for initial staging and treatment response evaluation of DLBCL were reviewed retrospectively. Baseline Dmax, maximum standardized uptake value, total summation of all metabolic tumor volumes (tMTV), and total summation of all total lesion glycolysis (tTLG) were measured. The treatment response was evaluated at the interim and end of first-line treatment (EOT) using the Deauville score (DS). FDG PET/CT parameters and other clinical factors including sex, age, serum lactate dehydrogenase (LDH) level, stage, performance status, and the International Prognostic Index (IPI) were analyzed to identify factors prognostic of the time to progression (TTP) and disease-specific survival (DSS). Results: A total of 63 patients were included. Univariate survival analysis identified Dmax (> 275 mm), tMTV (> 180 mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) as significant predictors of poor TTP. Serum LDH level (> 640 IU/L), IPI (≥ 4), tMTV (> 180 mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) were significant predictors of DSS. After multivariate survival analysis, Dmax (P = 0.008) and EOT DS (P = 0.005) were independent predictors of TTP. EOT DS was an independent predictor of DSS (P = 0.029). Conclusions: Dmax at the time of diagnosis and the EOT response assessed by FDG PET/CT provide useful prognostic information additive to the IPI in patients with DLBCL.

FDG PET/CT to Predict Recurrence of Early Breast Invasive Ductal Carcinoma.

This study investigated the prognostic value of FDG PET/CT radiomic features for predicting recurrence in patients with early breast invasive ductal carcinoma (IDC). The medical records of consecutive patients who were newly diagnosed with primary breast IDC after curative surgery were reviewed. Patients who received any neoadjuvant treatment before surgery were not included. FDG PET/CT radiomic features, such as a maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), skewness, kurtosis, entropy, and uniformity, were measured for the primary breast tumor using LIFEx software to evaluate recurrence-free survival (RFS). A total of 124 patients with early breast IDC were evaluated. Eleven patients had a recurrence (8.9%). Univariate survival analysis identified large tumor size (>2 cm, p = 0.045), high Ki-67 expression (≥30%, p = 0.017), high AJCC prognostic stage (≥II, p = 0.044), high SUVmax (≥5.0, p = 0.002), high MTV (≥3.25 mL, p = 0.044), high TLG (≥10.5, p = 0.004), and high entropy (≥3.15, p = 0.003) as significant predictors of poor RFS. After multivariate survival analysis, only high MTV (p = 0.045) was an independent prognostic predictor. Evaluation of the MTV of the primary tumor by FDG PET/CT in patients with early breast IDC provides useful prognostic information regarding recurrence.

Association of True Positivity with Serum Prostate-Specific Antigen Levels and Other Clinical Factors in Indeterminate PSMA-RADS-3A Lesions Identified on 18F-DCFPyL PET/CT Scans.

The use of prostate-specific membrane antigen targeted PET imaging for the evaluation of prostate cancer has increased significantly in the last couple of decades. When evaluating these imaging findings based on the PSMA reporting and data system version 1.0, which categorize lesions based on their likelihood of prostate cancer involvement, PSMA-RADS-3A lesions are commonly seen, which are indeterminate for the presence of disease. A total of 28 patients with 171 PSMA-RADS-3A lesions on 18F-DCFPyL PET/CT scans from June 2016 to May 2017 who had follow-up cross-sectional imaging over time were included in this study. The PSA levels of patients with PSMA-RADS-3A lesions were categorized into four groups, 0-0.2, 0.2-1, 1-2, and >2 ng/mL. The pre-operative Gleason score of these patients was categorized into two groups, Gleason score < 7 or ≥7. The median age for these patients was 72.5 years (range 59-81). The median PSA value for patients with positive lesions was significantly higher than those with negative lesions (5.8 ng/mL vs. 0.2 ng/mL, p < 0.0001). The lesion positivity rate was significantly higher in patients with PSA > 1 ng/mL (18.2% vs. 81.9%, p < 0.001). On ROC analysis, the highest classification accuracy was seen at PSA ≥ 0.6 ng/mL of 80.12% (95% CI = 73.69-86.16%), and the area under the curve was 71.32% (95% CI = 61.9-80.7%, p < 0.0001). A total of 96.4% (108/112) of patients with positive lesions and 86.4% (51/59) of patients with negative lesions had a PSMA-RADS-4/5 lymph node on the initial 18F-DCFPyL PET/CT scan (p = 0.02). In patients with a Gleason score ≥ 7, the presence of positive PSMA-RADS-3A lesions was higher, compared to negative PSMA-RADS-3A lesions (p = 0.049). Higher PSA levels in patients with PSMA-RADS-3A lesions can point towards the presence of true positivity. PSA levels may be considered in deciding whether to call an indeterminate lesion on PSMA PET.

Deep learning and radiomics framework for PSMA-RADS classification of prostate cancer on PSMA PET.

BACKGROUND: Accurate classification of sites of interest on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) images is an important diagnostic requirement for the differentiation of prostate cancer (PCa) from foci of physiologic uptake. We developed a deep learning and radiomics framework to perform lesion-level and patient-level classification on PSMA PET images of patients with PCa. METHODS: This was an IRB-approved, HIPAA-compliant, retrospective study. Lesions on [18F]DCFPyL PET/CT scans were assigned to PSMA reporting and data system (PSMA-RADS) categories and randomly partitioned into training, validation, and test sets. The framework extracted image features, radiomic features, and tissue type information from a cropped PET image slice containing a lesion and performed PSMA-RADS and PCa classification. Performance was evaluated by assessing the area under the receiver operating characteristic curve (AUROC). A t-distributed stochastic neighbor embedding (t-SNE) analysis was performed. Confidence and probability scores were measured. Statistical significance was determined using a two-tailed t test. RESULTS: PSMA PET scans from 267 men with PCa had 3794 lesions assigned to PSMA-RADS categories. The framework yielded AUROC values of 0.87 and 0.90 for lesion-level and patient-level PSMA-RADS classification, respectively, on the test set. The framework yielded AUROC values of 0.92 and 0.85 for lesion-level and patient-level PCa classification, respectively, on the test set. A t-SNE analysis revealed learned relationships between the PSMA-RADS categories and disease findings. Mean confidence scores reflected the expected accuracy and were significantly higher for correct predictions than for incorrect predictions (P < 0.05). Measured probability scores reflected the likelihood of PCa consistent with the PSMA-RADS framework. CONCLUSION: The framework provided lesion-level and patient-level PSMA-RADS and PCa classification on PSMA PET images. The framework was interpretable and provided confidence and probability scores that may assist physicians in making more informed clinical decisions.