Prognostic significance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with T2N1 hormone receptor-positive, ERBB2-negative breast cancer who underwent adjuvant chemotherapy.

PURPOSE: To determine whether tumor uptake of 18F-fluorodeoxyglucose (18F-FDG) is associated with invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive ERBB2-negative early-stage breast cancer treated with adjuvant chemotherapy. METHODS: This is a single-center cohort study of women with breast cancer who underwent surgery between 2008 and 2015 at Asan Medical Center, Seoul, Korea. Patients were enrolled if they were diagnosed with HR-positive ERBB2-negative breast cancer with histology of invasive ductal carcinoma, had an American Joint Committee on Cancer pathologic tumor stage of T2N1 with 1-3 positive axillary nodes, underwent preoperative 18F-FDG positron emission tomography/computed tomography (PET/CT), and underwent breast cancer surgery followed by anthracycline- or taxane-based adjuvant chemotherapy. The primary outcome measure was IDFS. The maximum standardized uptake value (SUVmax) was dichotomized using a predefined cut-off of 4.14. RESULTS: A total of 129 patients were included. The median follow-up period for IDFS in those without recurrence was 82 months (interquartile range, 65-106). Multivariable Cox analysis showed that SUVmax was independently associated with IDFS [adjusted hazard ratio 2.49; 95% confidence interval (CI), 1.06-5.84]. Ten-year IDFS estimates via the Kaplan-Meier method were 0.60 (95% CI, 0.42-0.74) and 0.82 (95% CI, 0.65-0.91) for high and low SUVmax groups, respectively. The overall association between SUVmax and IDFS appeared to be consistent across subgroups divided according to age, progesterone receptor status, histologic grade, or presence of lymphovascular invasion. CONCLUSION: High SUVmax on preoperative 18F-FDG PET/CT was independently associated with reduced long-term IDFS in T2N1 HR-positive ERBB2-negative breast cancer patients who underwent adjuvant chemotherapy.

Diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study.

BACKGROUND: A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol (18F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer. METHODS: We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative 18F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body 18F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of 18F-FES, with dosing primarily determined by radiation dosimetry analysis. 18F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received 18F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received 18F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569. FINDINGS: Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the 18F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive 18F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative 18F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with 18F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded. INTERPRETATION: The high negative percent agreement between 18F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive 18F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include 18F-FES PET-CT when retesting oestrogen receptor status is not feasible. FUNDING: Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.

Physical exercise enhances adult cortical plasticity in a neonatal rat model of hypoxic-ischemic injury: Evidence from BOLD-fMRI and electrophysiological recordings.

Neuroplasticity is considered essential for recovery from brain injury in developing brains. Recent studies indicate that it is especially effective during early postnatal development and during the critical period. The current study used functional magnetic resonance imaging (fMRI) and local field potential (LFP) electrophysiological recordings in rats that experienced neonatal hypoxic-ischemic (HI) injury during the critical period to demonstrate that physical exercise (PE) can improve cortical plasticity even when performed during adulthood, after the critical period. We investigated to what extent the blood oxygen level-dependent (BOLD)-fMRI responses were increased in the contralesional spared cortex, and how these increases were related to the LFP electrophysiological measurements and the functional outcome. The balance of excitation and inhibition was assessed by measuring excitatory and inhibitory postsynaptic currents in stellate cells in the primary somatosensory (S1) cortex, which was compared with the BOLD-fMRI responses in the contralesional S1 cortex. The ratio of inhibitory postsynaptic current (IPSC) to excitatory postsynaptic current (EPSC) at the thalamocortical (TC) input to the spared S1 cortex was significantly increased by PE, which is consistent with the increased BOLD-fMRI responses and improved functional outcome. Our data clearly demonstrate in an experimental rat model of HI injury during the critical period that PE in adulthood enhances neuroplasticity and suggest that enhanced feed-forward inhibition at the TC input to the S1 cortex might underlie the PE-induced amelioration of the somatosensory deficits caused by the HI injury. In summary, the results of the current study indicate that PE, even if performed beyond the critical period or during adulthood, can be an effective therapy to treat neonatal brain injuries, providing a potential mechanism for the development of a potent rehabilitation strategy to alleviate HI-induced neurological impairments.

3'-Deoxy-3'-18F-Fluorothymidine and 18F-Fluorodeoxyglucose positron emission tomography for the early prediction of response to Regorafenib in patients with metastatic colorectal cancer refractory to all standard therapies.

PURPOSE: The purpose of this study was to evaluate the value of 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for early prediction of standard anatomic response and survival outcomes in patients with metastatic colorectal cancer (mCRC) receiving Regorafenib. METHODS: Sixty-eight patients with mCRC refractory to standard cytotoxic chemotherapy were enrolled and received Regorafenib (160 mg/day on days 1-21, following a 7-day break). Standard anatomical response was evaluated every 8 weeks. Both scans were performed before and on day 21 of Regorafenib. RESULTS: Of the 61 patients included in per-protocol analysis, complete response was not observed, but partial response was observed in 8.2% (n = 5), stable disease in 67.2% (n = 41), and progressive disease in 24.6% (n = 15). The objective response rate was 8.2% and disease control rate 75.4%. Five responders (8.2%) and 13 non-responders (21.3%) met the CT and 18F-FLT PET/CT criteria (maximum standardized uptake value decrease ≥ 10.6% for responders). Forty-three (70.5%) exhibited discordant responses on CT and 18F-FLT PET/CT (McNemar test, P < 0.001). At a median follow-up of 8.9 months, median progression-free survival (PFS) and median overall survival (OS) were 3.6 months (95% confidence interval [CI], 3.34-3.80 months) and 8.5 months (95% CI, 6.95-10.10 months), respectively. Comparison of PFS and OS according to 18F-FLT PET/CT response revealed slightly longer PFS (P = 0.015) in responders, but the correlation with OS was not significant. The PET Response Criteria in Solid Tumours (PERCIST) of 18F-FDG PET/CT revealed differences in PFS and OS between partial metabolic response (PMR) and non-PMR (P = 0.048 and P = 0.014, respectively), and between progressive metabolic disease (PMD) and non-PMD (P = 0.189 and P = 0.007, respectively). CONCLUSIONS: Survival outcome was significantly associated with PERCIST using 18F-FDG PET/CT but the change of 18F-FLT uptake was only slightly associated with PFS. 18F-FDG PET/CT can be used as imaging biomarker to predict clinical outcomes early in patients with mCRC receiving Regorafenib.

Feasibility of dynamic stress 201Tl/rest 99mTc-tetrofosmin single photon emission computed tomography for quantification of myocardial perfusion reserve in patients with stable coronary artery disease.

PURPOSE: We evaluated the feasibility of dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging using a cardiac camera equipped with cadmium-zinc-telluride detectors for the quantification of myocardial perfusion reserve (MPR). METHODS: Subjects with stable known or suspected coronary artery disease (CAD) who had undergone or were scheduled to undergo fractional flow reserve (FFR) measurement were prospectively enrolled. Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging was performed using a dedicated multiple pinhole SPECT camera with cadmium-zinc-telluride detectors. MPR was derived using Corridor4DM software. RESULTS: A total of 34 subjects were enrolled (25 men and 9 women; mean age 60.4 years). FFR was measured in 65 coronary arteries with intermediate lesions. The average global MPR was 2.58 ± 1.03. Global MPR was associated with the extent of CAD (P = 0.028) and global summed stress score (r = -0.60, P < 0.001). Regional MPR showed a significant correlation with diameter stenosis (r = -0.57, P < 0.001), minimum lumen diameter (r = 0.50, P < 0.001), summed stress score (r = -0.52, P < 0.001) and FFR (r = 0.52, P < 0.001). The area under the receiver operating characteristic curve of MPR for the diagnosis of functionally significant stenosis (FFR ≤0.8) was 0.79 (P < 0.001). The sensitivity and specificity of regional MPR were 67% and 83%, respectively, using a cut-off value of 2.0. CONCLUSION: Dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT imaging and quantification of MPR is feasible in patients with stable CAD. The preliminary results of this study in a small number of patients require confirmation in a larger cohort to determine their implications for bolstering the role of SPECT imaging in the diagnosis and risk prediction of CAD.

The Value of Preoperative Positron Emission Tomography/Computed Tomography in Node-Negative Endometrial Cancer on Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to investigate the value of [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in predicting lymph node status in node-negative endometrial cancer on preoperative magnetic resonance imaging (MRI). METHODS: Patients with endometrial cancer who underwent both preoperative MRI and FDG-PET/CT followed by hysterectomy and lymphadenectomy were initially included. We then enrolled patients with MRI-defined node-negative disease (lymph nodes <1 cm in the short-axis diameter, or no visible lymph node). Histologic examination was the gold standard for lymph node metastasis diagnosis. The diagnostic performance of FDG-PET/CT in predicting lymph node metastasis was calculated in patient-by-patient and lymph node station-by-station analyses. RESULTS: On preoperative MRI, 362 patients had no lymph node metastasis. All patients underwent pelvic lymph node dissection and 118 patients underwent further para-aortic lymph node dissection. From 2099 lymph node stations, 10,238 lymph nodes were retrieved. Twenty-seven patients (7.5%) had lymph node metastasis in 49 lymph node stations (2.3%) on pathologic examination. FDG-PET/CT identified lymph node metastasis in five patients (18.5%) and eight lymph node stations (16.3%). The median diameter of false-negative metastatic lymph nodes was 6 mm (range 1-22) in the long axis and 3 mm (range 1-11) in the short axis. For para-aortic lymph nodes, FDG-PET/CT diagnosed 2 of 11 patients (18.1%) with para-aortic lymph node metastasis, and 3 of 12 para-aortic lymph node stations (25%) with metastasis. CONCLUSION: Preoperative FDG-PET/CT has low value in predicting lymph node metastasis in node-negative endometrial cancer on preoperative MRI.

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats.

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel-based analysis are highly dependent on the user-hypothesis and parameter settings for implementation. In contrast, tract-based spatial statistics (TBSS) allows for reliable voxel-wise analysis via the projection of diffusion-derived parameters onto an alignment-invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI-derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2 h to 6 weeks after experimental focal ischemic stroke in rats (N = 6). FA values remained unchanged 2-4 h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24 h to 2 weeks post-stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6 weeks post-stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6 weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo-normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.

Comparison of MRI and PET-CT in detecting the loco-regional recurrence of soft tissue sarcomas during surveillance.

OBJECTIVE: To investigate the diagnostic performance of MRI and PET-CT for the detection of loco-regional recurrences after soft tissue sarcoma (STS) excision. MATERIALS AND METHODS: From Dec 2003 to Aug 2014, 394 patients with STSs, who were included in the electronic patient registry for initial or repeated surgery at our hospital, were retrospectively reviewed. We identified 152 patients who underwent regular postoperative follow-ups with both MRI and PET-CT, obtained within a 3 month period of each other. We analyzed differences in the performance of MRI and PET-CT for the diagnosis of loco-regional recurrences using McNemar's test. The receiver-operating characteristic curves and calculations of the area under the curve were used. RESULTS: Twenty patients were found to have a loco-regional recurrence after tumor excision. For MRI and PET-CT, the sensitivities were 90.0 and 95.0 %, and the specificities 97.7 and 95.5 %, respectively, with positive predictive values of 85.7 and 76.0 % and negative predictive values of 98.5 and 99.2 %, respectively. No significant difference was detected between the sensitivities of MRI and PET-CT (p = 0.125). The area under the receiver-operating characteristic curve for PET-CT (0.952) was not significantly greater than that for MRI (0.939; p = 0.6). CONCLUSION: MRI of the area of interest is recommended for evaluation of tumor recurrence after surgical excision of STS. PET-CT was shown to be effective for detection of STS recurrence, and comparable to MRI. However, if PET-CT or MRI findings are inconclusive, the other modality may be helpful in differentiating tumor recurrence from post-therapeutic tissue change.

Detection of internal mammary lymph node metastasis with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with stage III breast cancer.

PURPOSE: The present study assessed the positive predictive value (PPV) of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of internal mammary node (IMN) metastasis in patients with clinical stage III breast cancer. METHODS: Patients who were diagnosed with clinical stage III breast cancer and underwent pretreatment (18)F-FDG PET/CT were retrospectively analyzed. The (18)F-FDG PET/CT scans were prospectively reviewed by two board-certified nuclear medicine physicians in a blinded manner. The intensities of IMNs were graded into four categories (no activity and lower, similar, and higher activities than that of the mediastinal blood pool). IMNs were measured from the combined CT (largest diameter of the short axis). Histologic data of the IMNs were obtained by ultrasonography-guided fine-needle aspiration biopsy or surgical excision. The PPV was calculated for pathologically confirmed IMNs. Visual grade, maximum standardized uptake values (SUVmax), and sizes were analyzed according to the pathology results. RESULTS: There were 249 clinical stage III breast cancer patients (age 48.0 ± 10.1 years, range 26-79 years) who had undergone initial (18)F-FDG PET/CT prior to treatment. Excluding 33 cases of stage IV breast cancer, 62 of 216 patients had visible IMNs on (18)F-FDG PET/CT, and histologic confirmation was obtained in 31 patients. There were 27 metastatic and four nonmetastatic nodes (PPV 87.1%). Metastatic nodes mostly presented with visual grade 3 (83.9%), and SUVmax and size were 3.5 ± 4.3 and 5.6 ± 2.0 mm, respectively. CONCLUSION: (18)F-FDG PET/CT has a high PPV for IMN metastasis in clinical stage III breast cancer, indicating the possibility of metastasis in IMNs with FDG uptake similar to/lower than that of the blood pool or small-sized nodes.

Evaluation of selective positron emission tomography template method for spatial normalization of amyloid imaging with 11C-Pittsburgh Compound B.

OBJECTIVE: Spatial normalization of C-Pittsburgh Compound B (PiB) images is challenging for an automatic quantitative analysis without magnetic resonance imaging (MRI) because of different distribution patterns between amyloid positive and negative images. To overcome this issue, we evaluated a selective positron emission tomography template (SPT) method. MATERIALS AND METHODS: Three sets of single positron emission tomography templates were created: PiB negative template, PiB positive template, and mixed template. Sixty-one patients with dementia were enrolled as the validation cohort. Magnetic resonance imaging-aided normalization method was used as a reference. The SPT method was based on visual classification (positive, negative, and equivocal). The optimal templates for each visual group were determined by correlation values and average percent errors (APEs) with MRI-aided normalization. The results of the SPT and the single template methods were compared with those of MRI-aided normalization in terms of correlation values, APEs, and concordance rates. RESULTS: The SPT (PiB negative template for the negative and equivocal groups and PiB positive template for the positive group) showed higher correlations and concordance rate and lower APEs with MRI-aided normalization than did the single template. CONCLUSIONS: Use of the SPT provides accurate normalization of amyloid images without MRI.

Erratum: A Patient With Fahr's Disease Who Presented Prominent Visuospatial Dysfunction.

[This corrects the article on p. 117 in vol. 22, PMID: 37545866.].

Fully Automatic Quantitative Measurement of Equilibrium Radionuclide Angiocardiography Using a Convolutional Neural Network.

PURPOSE: The aim of this study was to generate deep learning-based regions of interest (ROIs) from equilibrium radionuclide angiography datasets for left ventricular ejection fraction (LVEF) measurement. PATIENTS AND METHODS: Manually drawn ROIs (mROIs) on end-systolic and end-diastolic images were extracted from reports in a Picture Archiving and Communications System. To reduce observer variability, preprocessed ROIs (pROIs) were delineated using a 41% threshold of the maximal pixel counts of the extracted mROIs and were labeled as ground-truth. Background ROIs were automatically created using an algorithm to identify areas with minimum counts within specified probability areas around the end-systolic ROI. A 2-dimensional U-Net convolutional neural network architecture was trained to generate deep learning-based ROIs (dlROIs) from pROIs. The model's performance was evaluated using Lin's concordance correlation coefficient (CCC). Bland-Altman plots were used to assess bias and 95% limits of agreement. RESULTS: A total of 41,462 scans (19,309 patients) were included. Strong concordance was found between LVEF measurements from dlROIs and pROIs (CCC = 85.6%; 95% confidence interval, 85.4%-85.9%), and between LVEF measurements from dlROIs and mROIs (CCC = 86.1%; 95% confidence interval, 85.8%-86.3%). In the Bland-Altman analysis, the mean differences and 95% limits of agreement of the LVEF measurements were -0.6% and -6.6% to 5.3%, respectively, for dlROIs and pROIs, and -0.4% and -6.3% to 5.4% for dlROIs and mROIs, respectively. In 37,537 scans (91%), the absolute LVEF difference between dlROIs and mROIs was <5%. CONCLUSIONS: Our 2-dimensional U-Net convolutional neural network architecture showed excellent performance in generating LV ROIs from equilibrium radionuclide angiography scans. It may enhance the convenience and reproducibility of LVEF measurements.

Deep learning-based measurement of split glomerular filtration rate with 99mTc-diethylenetriamine pentaacetic acid renal scan.

PURPOSE: To develop a deep learning (DL) model for generating automated regions of interest (ROIs) on 99mTc-diethylenetriamine pentaacetic acid (DTPA) renal scans for glomerular filtration rate (GFR) measurement. METHODS: Manually-drawn ROIs retrieved from a Picture Archiving and Communications System were used as ground-truth (GT) labels. A two-dimensional U-Net convolutional neural network architecture with multichannel input was trained to generate DL ROIs. The agreement between GFR values from GT and DL ROIs was evaluated using Lin's concordance correlation coefficient (CCC) and slope coefficients for linear regression analyses. Bias and 95% limits of agreement (LOA) were assessed using Bland-Altman plots. RESULTS: A total of 24,364 scans (12,822 patients) were included. Excellent concordance between GT and DL GFR was found for left (CCC 0.982, 95% confidence interval [CI] 0.981-0.982; slope 1.004, 95% CI 1.003-1.004), right (CCC 0.969, 95% CI 0.968-0.969; slope 0.954, 95% CI 0.953-0.955) and both kidneys (CCC 0.978, 95% CI 0.978-0.979; slope 0.979, 95% CI 0.978-0.979). Bland-Altman analysis revealed minimal bias between GT and DL GFR, with mean differences of - 0.2 (95% LOA - 4.4-4.0), 1.4 (95% LOA - 3.5-6.3) and 1.2 (95% LOA - 6.5-8.8) mL/min/1.73 m² for left, right and both kidneys, respectively. Notably, 19,960 scans (81.9%) showed an absolute difference in GFR of less than 5 mL/min/1.73 m². CONCLUSION: Our DL model exhibited excellent performance in the generation of ROIs on 99mTc-DTPA renal scans. This automated approach could potentially reduce manual effort and enhance the precision of GFR measurement in clinical practice.

Associations of cardiovascular and diabetes-related risk factors with myocardial perfusion reserve assessed by 201Tl/99mTc-tetrofosmin single-photon emission computed tomography in patients with diabetes mellitus and stable coronary artery disease.

We aimed to examine the associations of cardiovascular risk factors with myocardial perfusion reserve (MPR) in patients with type 2 diabetes and stable coronary artery disease. The study patients were retrospectively identified from a database of patients with diabetes and stable coronary artery disease at Asan Medical Center (Seoul, Republic of Korea), covering the period from 2017 to 2019. The primary outcome variable was MPR assessed by dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT. Univariable and stepwise multivariable analyses were performed to assess the associations of cardiovascular risk factors with MPR. A total of 276 patients (236 men and 40 women) were included. The median global MPR was 2.4 (interquartile range 1.9-3.0). Seventy-five (27.2%) patients had an MPR < 2.0. Multivariable linear regression showed that smoking (ß = - 0.44, 95% confidence interval - 0.68 to - 0.21, P < 0.001), hypertension (ß = - 0.24, 95% confidence interval - 0.47 to - 0.02, P = 0.033), and summed difference score (ß = - 0.05, 95% confidence interval - 0.07 to - 0.03, P < 0.001) were independently associated with MPR. Abnormal MPR (< 2.0) was associated with a higher incidence of cardiac death or myocardial infarction (P = 0.034). MPR assessed by dynamic stress 201Tl/rest 99mTc-tetrofosmin SPECT was impaired in a large cohort of patients with diabetes. After adjusting for risk variables, including standard myocardial perfusion imaging characteristics, smoking, and hypertension were associated with MPR. Our results may aid in identifying patients with impaired MPR and stratifying patients with type 2 diabetes.

Association between tumor 18F-fluorodeoxyglucose metabolism and survival in women with estrogen receptor-positive, HER2-negative breast cancer.

We examined whether 18F-fluorodeoxyglucose metabolism is associated with distant relapse-free survival (DRFS) and overall survival (OS) in women with estrogen receptor (ER)-positive, HER2-negative breast cancer. This was a cohort study examining the risk factors for survival that had occurred at the start of the study. A cohort from Asan Medical Center, Korea, recruited between November 2007 and December 2014, was included. Patients received anthracycline-based neoadjuvant chemotherapy. The maximum standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) was measured. The analysis included 466 women. The median (interquartile range) follow-up period without distant metastasis or death was 6.2 (5.3-7.6) years. Multivariable analysis of hazard ratio (95% confidence interval [CI]) showed that the middle and high tertiles of SUV were prognostic for DRFS (2.93, 95% CI 1.62-5.30; P < 0.001) and OS (4.87, 95% CI 1.94-12.26; P < 0.001). The 8-year DRFS rates were 90.7% (95% CI 85.5-96.1%) for those in the low tertile of maximum SUV vs. 73.7% (95% CI 68.0-79.8%) for those in the middle and high tertiles of maximum SUV. 18F-fluorodeoxyglucose PET/CT may assess the risk of distant metastasis and death in ER-positive, HER2-negative patients.

PET Imaging of System xC - in Immune Cells for Assessment of Disease Activity in Mice and Patients with Inflammatory Bowel Disease.

We aimed to explore whether the imaging of antiporter system xC - of immune cells with (4S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system xC - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68+xCT+ and CD3+xCT+ cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68+xCT+ cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system xC - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18F-FSPG PET imaging of system xC - activity may noninvasively assess the IBD activity.

Assessment of naive indolent lymphoma using whole-body diffusion-weighted imaging and T2-weighted MRI: results of a prospective study in 30 patients.

BACKGROUND: We prospectively evaluated the diagnostic utility of whole-body diffusion-weighted imaging with background body signal suppression and T2-weighted short-tau inversion recovery MRI (WB-DWIBS/STIR) for the pretherapeutic staging of indolent lymphoma in 30 patients. METHODS: This prospective study included 30 treatment-naive patients with indolent lymphomas who underwent WB-DWIBS/STIR and conventional imaging workup plus biopsy. The pretherapeutic staging agreement, sensitivity, and specificity of WB-DWIBS/STIR were investigated with reference to the multimodality and multidisciplinary consensus review for nodal and extranodal lesions excluding bone marrow. RESULTS: In the pretherapeutic staging, WB-DWIBS/STIR showed very good agreement (κ = 0.96; confidence interval [CI], 0.88-1.00), high sensitivity (93.4-95.1%), and high specificity (99.0-99.4%) for the whole-body regions. These results were similar to those of 18F-FDG-PET/CT, except for the sensitivity for extranodal lesions. For extranodal lesions, WB-DWIBS/STIR showed higher sensitivity compared to 18F-FDG-PET/CT for the whole-body regions (94.9-96.8% vs. 79.6-86.3%, P = 0.058). CONCLUSION: WB-DWIBS/STIR is an effective modality for the pretherapeutic staging of indolent lymphoma, and it has benefits when evaluating extranodal lesions, compared with 18F-FDG-PET/CT.

Prognostic Factors of Quantitative Lymphoscintigraphic Findings in Patients with Breast Cancer-Related Lymphedema.

Background: To evaluate the usefulness of quantitative findings of pretherapy lymphoscintigraphy in predicting the effects of complex decongestive therapy (CDT) in patients with upper extremity lymphedema after breast cancer treatment. Methods and Results: We retrospectively analyzed patients with unilateral breast cancer-related lymphedema (BCRL) who underwent pretherapy lymphoscintigraphy and completed 2 weeks of CDT. A total of 18 patients with unilateral BCRL clinical stage II underwent 30-minute sessions of CDT five times per week for 2 weeks. The quantitative asymmetry index (QAI) of the upper extremity, axillary lymph node (LN) uptake, and axillary plus supraclavicular LN uptake from lymphoscintigraphy were calculated. The volume of lymphedema was calculated by percentage excess volume (PEV) at initial and posttreatment. The CDT response was assessed using percentage reduction in excess volume (PREV). Correlation analyses were conducted using Kendall tau rank correlation. There was positive correlation between upper extremity QAI at 2 hours and initial PEV. Negative correlations were found between axillary LN QAI at 1, 2 hours, and initial PEV, and between axillary plus supraclavicular LN QAI at 1, 2 hours, and initial PEV. The PREV showed a positive correlation with axillary LN QAI at 2 hours after injection (tau-b = 0.354, p = 0.041). Conclusion: Quantitative findings of pretherapy lymphoscintigraphy have potential value for use in predicting the response to CDT in patients with upper extremity lymphedema after breast cancer treatment. Using QAIs from lymphoscintigraphy, we could estimate the excess volume of lymphedema.

Clinicopathological characteristics of primary central nervous system lymphoma with low 18F-fludeoxyglucose uptake on brain positron emission tomography.

Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake.We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0-2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions.Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007).This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.

Comparison of diagnostic sensitivity of [18F]fluoroestradiol and [18F]fluorodeoxyglucose positron emission tomography/computed tomography for breast cancer recurrence in patients with a history of estrogen receptor-positive primary breast cancer.

BACKGROUND: To compare the diagnostic sensitivity of [18F]fluoroestradiol ([18F]FES) and [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) for breast cancer recurrence in patients with estrogen receptor (ER)-positive primary breast cancer. METHODS: Our database of consecutive patients enrolled in a previous prospective cohort study to assess [18F]FES PET/CT was reviewed to identify eligible patients who had ER-positive primary breast cancer with suspected first recurrence at presentation and who underwent [18F]FDG PET/CT. The sensitivity of qualitative [18F]FES and [18F]FDG PET/CT interpretations was assessed, comparing them with histological diagnoses. RESULTS: Of the 46 enrolled patients, 45 were confirmed as having recurrent breast cancer, while one was diagnosed with chronic granulomatous inflammation. Forty (89%) patients were ER-positive, four (9%) were ER-negative, and one (2%) patient did not undergo an ER assay. The sensitivity of [18F]FES PET/CT was 71.1% (32/45, 95% CI, 55.7-83.6), while that of [18F]FDG PET/CT was 80.0% (36/45, 95% CI, 65.4-90.4) with a threshold of positive interpretation, and 93.3% (42/45, 95% CI, 81.7-98.6) when a threshold of equivocal was used. There was no significant difference in sensitivity between [18F]FES and [18F]FDG PET/CT (P = 0.48) with a threshold of positive [18F]FDG uptake, but the sensitivity of [18F]FDG was significantly higher than [18F]FES (P = 0.013) with a threshold of equivocal [18F]FDG uptake. One patient with a benign lesion showed negative [18F]FES but positive [18F]FDG uptake. CONCLUSIONS: The restaging of patients who had ER-positive primary breast cancer and present with recurrent disease may include [18F]FES PET/CT as an initial test when standard imaging studies are equivocal or suspicious.