Distinct subtypes of spatial brain metabolism patterns in Alzheimer's disease identified by deep learning-based FDG PET clusters.

PURPOSE: Alzheimer's disease (AD) is a heterogeneous disease that presents a broad spectrum of clinicopathologic profiles. To date, objective subtyping of AD independent of disease progression using brain imaging has been required. Our study aimed to extract representations of unique brain metabolism patterns different from disease progression to identify objective subtypes of AD. METHODS: A total of 3620 FDG brain PET images with AD, mild cognitive impairment (MCI), and cognitively normal (CN) were obtained from the ADNI database from 1607 participants at enrollment and follow-up visits. A conditional variational autoencoder model was trained on FDG brain PET images of AD patients with the corresponding condition of AD severity score. The k-means algorithm was applied to generate clusters from the encoded representations. The trained deep learning-based cluster model was also transferred to FDG PET of MCI patients and predicted the prognosis of subtypes for conversion from MCI to AD. Spatial metabolism patterns, clinical and biological characteristics, and conversion rate from MCI to AD were compared across the subtypes. RESULTS: Four distinct subtypes of spatial metabolism patterns in AD with different brain pathologies and clinical profiles were identified: (i) angular, (ii) occipital, (iii) orbitofrontal, and (iv) minimal hypometabolic patterns. The deep learning model was also successfully transferred for subtyping MCI, and significant differences in frequency (P < 0.001) and risk of conversion (log-rank P < 0.0001) from MCI to AD were observed across the subtypes, highest in S2 (35.7%) followed by S1 (23.4%). CONCLUSION: We identified distinct subtypes of AD with different clinicopathologic features. The deep learning-based approach to distinguish AD subtypes on FDG PET could have implications for predicting individual outcomes and provide a clue to understanding the heterogeneous pathophysiology of AD.

Phase 1 Study of No-Carrier Added 177Lu-DOTATATE (SNU-KB-01) in Patients with Somatostatin Receptor-Positive Neuroendocrine Tumors: The First Clinical Trial of Peptide Receptor Radionuclide Therapy in Korea.

PURPOSE: To provide a wider choice of treatment opportunities for patients with neuroendocrine tumor (NET) in Korea, we have conducted a phase 1, open-label, single-arm, dose-escalation study of SNU-KB-01, a no-carrier added (NCA) 177Lu-labeled DOTATATE. MATERIALS AND METHODS: Seven patients with inoperable, progressive, metastatic, or locally advanced, somatostatin receptor-positive NET with Ki67 index ≤ 20% were enrolled according to the rolling six design. The study consisted of two cohorts to receive 4 cycles of SNU-KB-01 every 8 weeks for the first dose of 5.55 GBq (n=3) and 7.40 GBq (n=4). We assessed the incidence of dose-limiting toxicity (DLT) and adverse event, absorbed dose of kidneys and bone marrow, and objective tumor response. RESULTS: Seven patients completed 4 cycles (21.3-30.1 GBq total dose) of SNU-KB-01. The mean absorbed doses to kidneys and bone marrow were 0.500 mGy/MBq and 0.053 mGy/MBq, respectively, and the total body effective dose was 0.115 mSv/MBq. No DLT was observed and the maximum tolerated dose was 7.40 GBq/cycle. Grade 3 thrombocytopenia occurred in one patient, but no other grade 3 or 4 major hematologic or renal toxicity was observed. The best objective response to SNU-KB-01 was partial response. Overall response rate was 42.9% and disease control rate was 85.7%. CONCLUSION: Treatment with 4 cycles of SNU-KB-01 was well tolerated and resulted in control of disease in most of the patients. Our results indicate SNU-KB-01, an NCA 177Lu-labeled DOTATATE, as a potentially safe and efficacious treatment option for NET patients in Korea.

Deep learning signature of brain [18F]FDG PET associated with cognitive outcome of rapid eye movement sleep behavior disorder.

An objective biomarker to predict the outcome of isolated rapid eye movement sleep behavior disorder (iRBD) is crucial for the management. This study aimed to investigate cognitive signature of brain [18F]FDG PET based on deep learning (DL) for evaluating patients with iRBD. Fifty iRBD patients, 19 with mild cognitive impairment (MCI) (RBD-MCI) and 31 without MCI (RBD-nonMCI), were prospectively enrolled. A DL model for the cognitive signature was trained by using Alzheimer's Disease Neuroimaging Initiative database and transferred to baseline [18F]FDG PET from the iRBD cohort. The results showed that the DL-based cognitive dysfunction score was significantly higher in RBD-MCI than in RBD-nonMCI. The AUC of ROC curve for differentiating RBD-MCI from RBD-nonMCI was 0.70 (95% CI 0.56-0.82). The baseline DL-based cognitive dysfunction score was significantly higher in iRBD patients who showed a decrease in CERAD scores during 2 years than in those who did not. Brain metabolic features related to cognitive dysfunction-related regions of individual iRBD patients mainly included posterior cortical regions. This work demonstrates that the cognitive signature based on DL could be used to objectively evaluate cognitive function in iRBD. We suggest that this approach could be extended to an objective biomarker predicting cognitive decline and neurodegeneration in iRBD.

Transforming Thyroid Cancer Diagnosis and Staging Information from Unstructured Reports to the Observational Medical Outcome Partnership Common Data Model.

BACKGROUND: Cancer staging information is an essential component of cancer research. However, the information is primarily stored as either a full or semistructured free-text clinical document which is limiting the data use. By transforming the cancer-specific data to the Observational Medical Outcome Partnership Common Data Model (OMOP CDM), the information can contribute to establish multicenter observational cancer studies. To the best of our knowledge, there have been no studies on OMOP CDM transformation and natural language processing (NLP) for thyroid cancer to date. OBJECTIVE: We aimed to demonstrate the applicability of the OMOP CDM oncology extension module for thyroid cancer diagnosis and cancer stage information by processing free-text medical reports. METHODS: Thyroid cancer diagnosis and stage-related modifiers were extracted with rule-based NLP from 63,795 thyroid cancer pathology reports and 56,239 Iodine whole-body scan reports from three medical institutions in the Observational Health Data Sciences and Informatics data network. The data were converted into the OMOP CDM v6.0 according to the OMOP CDM oncology extension module. The cancer staging group was derived and populated using the transformed CDM data. RESULTS: The extracted thyroid cancer data were completely converted into the OMOP CDM. The distributions of histopathological types of thyroid cancer were approximately 95.3 to 98.8% of papillary carcinoma, 0.9 to 3.7% of follicular carcinoma, 0.04 to 0.54% of adenocarcinoma, 0.17 to 0.81% of medullary carcinoma, and 0 to 0.3% of anaplastic carcinoma. Regarding cancer staging, stage-I thyroid cancer accounted for 55 to 64% of the cases, while stage III accounted for 24 to 26% of the cases. Stage-II and -IV thyroid cancers were detected at a low rate of 2 to 6%. CONCLUSION: As a first study on OMOP CDM transformation and NLP for thyroid cancer, this study will help other institutions to standardize thyroid cancer-specific data for retrospective observational research and participate in multicenter studies.

Phase I Clinical Trial of Prostate-Specific Membrane Antigen-Targeting 68Ga-NGUL PET/CT in Healthy Volunteers and Patients with Prostate Cancer.

OBJECTIVE: 68Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68Ga-NGUL in healthy volunteers and the lesion detection rate of 68Ga-NGUL in patients with prostate cancer. MATERIALS AND METHODS: We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68Ga-NGUL (2 MBq/kg; 96-165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. RESULTS: All 12 participants (six healthy adults aged 31-32 years and six prostate cancer patients aged 57-81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68Ga-NGUL PET/CT or conventional imaging. Among them, 68Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. CONCLUSION: 68Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68Ga-NGUL is a valuable option for prostate cancer imaging.

Second primary malignancy risk in thyroid cancer and matched patients with and without radioiodine therapy analysis from the observational health data sciences and informatics.

PURPOSE: Risk of second primary malignancy (SPM) after radioiodine (RAI) therapy has been continuously debated. The aim of this study is to identify the risk of SPM in thyroid cancer (TC) patients with RAI compared with TC patients without RAI from matched cohort. METHODS: Retrospective propensity-matched cohorts were constructed across 4 hospitals in South Korea via the Observational Health Data Science and Informatics (OHDSI), and electrical health records were converted to data of common data model. TC patients who received RAI therapy constituted the target group, whereas TC patients without RAI therapy constituted the comparative group with 1:1 propensity score matching. Hazard ratio (HR) by Cox proportional hazard model was used to estimate the risk of SPM, and meta-analysis was performed to pool the HRs. RESULTS: Among a total of 24,318 patients, 5,374 patients from each group were analyzed (mean age 48.9 and 49.2, women 79.4% and 79.5% for target and comparative group, respectively). All hazard ratios of SPM in TC patients with RAI therapy were ≤ 1 based on 95% confidence interval(CI) from full or subgroup analyses according to thyroid cancer stage, time-at-risk period, SPM subtype (hematologic or non-hematologic), and initial age (< 30 years or ≥ 30 years). The HR within the target group was not significantly higher (< 1) in patients who received over 3.7 GBq of I-131 compared with patients who received less than 3.7 GBq of I-131 based on 95% CI. CONCLUSION: There was no significant difference of the SPM risk between TC patients treated with I-131 and propensity-matched TC patients without I-131 therapy.

Comparison of endoscopically determined gross tumor volume and metabolic tumor volume in esophageal cancer.

ABSTRACT: The purpose of this study is to compare the longitudinal location of endoscopically-defined gross tumor volume (GTV) and positron emission tomography-based metabolic tumor volume (MTV) of esophageal cancer.A retrospective review of medical records was performed of the nine patients who underwent endoscopic placement of fiducial markers for radiotherapy of esophageal squamous cell carcinoma. Endoscopic hemoclips were used as the fiducial markers, and GTV was newly delineated solely based on the locations of the fiducial markers. The standardized uptake value (SUV) threshold corresponding to the superior and inferior borders of GTV was defined as the highest threshold that made MTV reach each border of GTV.The median fixed relative and absolute thresholds were 32% and 3.8, respectively. The coefficient of variation of the threshold values was 0.781 for the fixed relative threshold method and 0.400 for the fixed absolute threshold method, indicating more consistent results from the fixed absolute threshold method. All but two GTV borders were included in MTV with a SUV threshold of 2.5. Esophageal tumors with a maximum SUV > 20 tended to have closer threshold values corresponding to the GTV borders to 2.5 (median 2.8 vs 3.6, P = .069).The fixed absolute threshold method was suitable for determining the MTV threshold for esophageal lesions. A SUV of 2.5 was appropriate for esophageal tumors with a maximum SUV > 20. Endoscopic hemoclips were stable enough for using as the fiducial marker.

Quantitative salivary gland SPECT/CT using deep convolutional neural networks.

Quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) using Tc-99m pertechnetate aids in evaluating salivary gland function. However, gland segmentation and quantitation of gland uptake is challenging. We develop a salivary gland SPECT/CT with automated segmentation using a deep convolutional neural network (CNN). The protocol comprises SPECT/CT at 20 min, sialagogue stimulation, and SPECT at 40 min post-injection of Tc-99m pertechnetate (555 MBq). The 40-min SPECT was reconstructed using the 20-min CT after misregistration correction. Manual salivary gland segmentation for %injected dose (%ID) by human experts proved highly reproducible, but took 15 min per scan. An automatic salivary segmentation method was developed using a modified 3D U-Net for end-to-end learning from the human experts (n = 333). The automatic segmentation performed comparably with human experts in voxel-wise comparison (mean Dice similarity coefficient of 0.81 for parotid and 0.79 for submandibular, respectively) and gland %ID correlation (R2 = 0.93 parotid, R2 = 0.95 submandibular) with an operating time less than 1 min. The algorithm generated results that were comparable to the reference data. In conclusion, with the aid of a CNN, we developed a quantitative salivary gland SPECT/CT protocol feasible for clinical applications. The method saves analysis time and manual effort while reducing patients' radiation exposure.

Head-to-Head Comparison of 68Ga-NOTA (68Ga-NGUL) and 68Ga-PSMA-11 in Patients with Metastatic Prostate Cancer: A Prospective Study.

68Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA)-targeting tracer used for PET/CT imaging. This study aimed to compare performance in the detection of primary and metastatic lesions and to compare biodistribution between 68Ga-NGUL and 68Ga-PSMA-11 in the same patients with prostate cancer. Methods: Eleven patients with metastatic prostate cancer were prospectively recruited. The quantitative tracer uptake was determined in normal organs and in primary and metastatic lesions. Results:68Ga-NGUL showed significantly lower normal-organ uptake and rapid urinary clearance. The number and sites of detected PSMA-positive primary and metastatic lesions were identical, and no significant quantitative uptake difference was observed. 68Ga-NGUL showed a relatively lower tumor-to-background ratio than 68Ga-PSMA-11. Conclusion: In a head-to-head comparison with 68Ga-PSMA-11, 68Ga-NGUL showed lower uptake in normal organs and similar performance in detecting PSMA-avid primary and metastatic lesions. 68Ga-NGUL could be a valuable option for PSMA imaging.

Basal and Acetazolamide Brain Perfusion SPECT in Internal Carotid Artery Stenosis.

Internal carotid artery (ICA) stenosis including Moyamoya disease needs revascularization when hemodynamic insufficiency is validated. Vascular reserve impairment was the key to find the indication for endarterectomy/bypass surgery in the atherosclerotic ICA stenosis and to determine the indication, treatment effect, and prognosis in Moyamoya diseases. Vascular reserve was quantitatively assessed by 1-day split-dose I-123 IMP basal/acetazolamide SPECT in Japan or by Tc-99m HMPAO SPECT in other countries using qualitative or semi-quantitative method. We summarized the development of 1-day basal/ acetazolamide brain perfusion SPECT for ICA stenosis, both quantitative and qualitative methods, and their methodological issues regarding (1) acquisition protocol; (2) qualitative assessment, either visual or deep learning-based; (3) clinical use for atherosclerotic ICA steno-occlusive diseases and mostly Moyamoya diseases; and (4) their impact on the choice of treatment options. Trials to use CT perfusion or perfusion MRI using contrast materials or arterial spin labeling were briefly discussed in their endeavor to use basal studies alone to replace acetazolamide-challenge SPECT. Theoretical and practical issues imply that basal perfusion evaluation, no matter how much sophisticated, will not disclose vascular reserve. Acetazolamide rarely causes serious adverse reactions but included fatality, and now, we need to monitor patients closely in acetazolamide-challenge studies.

Spleen Scan for 68Ga-DOTATOC PET-Positive Pancreatic Tail Lesion: Differential Diagnosis of Neuroendocrine Tumor from Accessory Spleen.

68Ga-DOTATOC PET/CT is widely used as a functional imaging technique in the detection and characterization of neuroendocrine tumors (NETs). Pancreatic NET and intrapancreatic accessory spleen (IPAS) have similar radiologic characteristics in anatomical imaging and usually show high uptake of 68Ga-DOTATOC. Thus, it is challenging to make a differential diagnosis between NET and IPAS when the tumor-like lesion is located in the pancreatic tail. Here, we present a case of 68Ga-DOTATOC PET-positive pancreatic tail lesion with high arterial enhancement on CT and MRI. Since 99mTc-labeled damaged red blood cell does not accumulate on NET, a negative spleen scan finding was a crucial diagnostic step to decide surgical resection, which was histologically proven as insulinoma. Our case shows a promising role of additional use of spleen scan with SPECT/CT for the differential diagnosis of 68Ga-DOTATOC PET-positive pancreatic NET from the accessory spleen.

Deep learning-based interpretation of basal/acetazolamide brain perfusion SPECT leveraging unstructured reading reports.

PURPOSE: Basal/acetazolamide brain perfusion single-photon emission computed tomography (SPECT) has been used to evaluate functional hemodynamics in patients with carotid artery stenosis. We aimed to develop a deep learning model as a support system for interpreting brain perfusion SPECT leveraging unstructured text reports. METHODS: In total, 7345 basal/acetazolamide brain perfusion SPECT images and their text reports were retrospectively collected. A long short-term memory (LSTM) network was trained using 500 randomly selected text reports to predict manually labeled structured information, including abnormalities of basal perfusion and vascular reserve for each vascular territory. Using this trained LSTM model, we extracted structured information from the remaining 6845 text reports to develop a deep learning model for interpreting SPECT images. The model was based on a 3D convolutional neural network (CNN), and the performance was tested on the other 500 cases by measuring the area under the receiver-operating characteristic curve (AUC). We then applied the model to patients who underwent revascularization (n = 33) to compare the estimated output of the CNN model for pre- and post-revascularization SPECT and clinical outcomes. RESULTS: The AUC of the LSTM model for extracting structured labels was 1.00 for basal perfusion and 0.99 for vascular reserve for all 9 brain regions. The AUC of the CNN model designed to identify abnormal perfusion was 0.83 for basal perfusion and 0.89 for vascular reserve. The output of the CNN model was significantly improved according to the revascularization in the target vascular territory, and its changes in brain territories were concordant with clinical outcomes. CONCLUSION: We developed a deep learning model to support the interpretation of brain perfusion SPECT by converting unstructured text reports into structured labels. This model can be used as a support system not only to identify perfusion abnormalities but also to provide quantitative scores of abnormalities, particularly for patients who require revascularization.

Clinical implication of 18F-NaF PET/computed tomography indexes of aortic calcification in coronary artery disease patients: correlations with cardiovascular risk factors.

OBJECTIVE: Vascular calcification is known to be associated with cardiovascular risk factors. Recently, F-NaF PET has been reported to be effective for detecting early and active vascular calcification. In this study, correlations between F-NaF PET/computed tomography (CT) findings and cardiovascular risk factors were investigated in patients with suspected coronary artery disease. PATIENTS AND METHODS: Forty patients with suspected coronary artery disease underwent F-NaF PET/CT. The maximum and overall burden of calcifying activity, and the overall burden of calcium deposition in the descending thoracic aorta (DTA) were measured on F-NaF PET/CT and they were compared with cardiovascular risk factors, particularly, with those related to metabolic syndrome. RESULTS: The maximum and overall burden of calcifying activity in DTA measured on F-NaF PET were significantly correlated with diabetes mellitus (P = 0.030 and 0.049, respectively) and serum HbA1c level (ρ = 0.433 and 0.344, respectively). In contrast, the overall burden of calcium deposition measured on CT was significantly correlated with hypertension (P < 0.001). The overall burden of calcium deposition was also significantly correlated with metabolic syndrome (P = 0.002) and 10-year cardiovascular disease risk score (P = 0.004) CONCLUSION: F-NaF uptake is closely related to diabetes mellitus, whereas aortic calcification on CT is closely related to hypertension. Although F-NaF uptake in DTA can be a potential prognostic factor, aortic calcification on CT is a more significant prognostic factor for overall cardiovascular risk than F-NaF uptake.

Comparative Analysis of Lung Perfusion Scan and SPECT/CT for the Evaluation of Functional Lung Capacity.

PURPOSE: This study aimed to compare lung perfusion scan with single photon emission computed tomography/computed tomography (SPECT/CT) for the evaluation of lung function and to elucidate the most appropriate modality for the prediction of postoperative lung function in patients with lung cancer. METHODS: A total of 181 patients underwent Tc-99m macroaggregated albumin lung perfusion scan and SPECT/CT to examine the ratio of diseased lung and diseased lobe. Forty-one patients with lung cancer underwent both preoperative and postoperative pulmonary function tests within 1 month to predict postoperative pulmonary function. Predicted postoperative forced expiratory volume in 1 s (ppoFEV1) was calculated by the % radioactivity of lung perfusion scan and SPECT, and the % volume of the residual lung, assessed on CT. RESULTS: The ratios of diseased lung as seen on lung perfusion scan and SPECT showed significant correlation, but neither modality correlated with CT. The ratios of the diseased lung and diseased lobe based on CT were higher than the ratios based on either perfusion scan or SPECT, because CT overestimated the function of the diseased area. The lobar ratio of both upper lobes was lower based on the perfusion scan than on SPECT but was higher for both lower lobes. Actual postoperative FEV1 showed significant correlation with ppoFEV1 based on lung perfusion SPECT and perfusion scan. CONCLUSIONS: We suggest SPECT/CT as the primary modality of choice for the assessment of the ratio of diseased lung area. Both perfusion scan and SPECT/CT can be used for the prediction of postoperative lung function.

Amyloid PET Quantification Via End-to-End Training of a Deep Learning.

PURPOSE: Although quantification of amyloid positron emission tomography (PET) is important for evaluating patients with cognitive impairment, its routine clinical use is hampered by complicated preprocessing steps and required MRI. Here, we suggested a one-step quantification based on deep learning using native-space amyloid PET images of different radiotracers acquired from multiple centers. METHODS: Amyloid PET data of the Alzheimer Disease Neuroimaging Initiative (ADNI) were used for this study. A training/validation consists of 850 florbetapir PET images. Three hundred sixty-six florbetapir and 89 florbetaben PET images were used as test sets to evaluate the model. Native-space amyloid PET images were used as inputs, and the outputs were standardized uptake value ratios (SUVRs) calculated by the conventional MR-based method. RESULTS: The mean absolute errors (MAEs) of the composite SUVR were 0.040, 0.060, and 0.050 of training/validation and test sets for florbetapir PET and a test set for florbetaben PET, respectively. The agreement of amyloid positivity measured by Cohen's kappa for test sets of florbetapir and florbetaben PET were 0.87 and 0.89, respectively. CONCLUSION: We suggest a one-step quantification method for amyloid PET via a deep learning model. The model is highly reliable to quantify the amyloid PET regardless of multicenter images and various radiotracers.

Minimum Standardized Uptake Value from Quantitative Bone Single-Photon Emission Computed Tomography/Computed Tomography for Evaluation of Femoral Head Viability in Patients with Femoral Neck Fracture.

PURPOSE: Bone single-photon emission computed tomography/computed tomography (SPECT/CT) has been widely used for evaluation of femoral head viability in patients with femoral neck fracture. The current study aimed to investigate utility of standardized uptake value (SUV) from quantitative bone SPECT/CT for assessment of femoral head viability. METHODS: From March 2015 to November 2018, quantitative bone SPECT/CT was performed in 9 patients with non-viable femoral head post femoral neck fracture and in 31 controls. Maximum (SUVmax), mean (SUVmean), and minimum standardized uptake values (SUVmin) were measured over femoral head and neck. Mann-Whitney U test with Bonferroni correction was used to compare SUVs of ipsilateral and contralateral femurs from femoral neck fracture patients with those of control femurs. RESULTS: As for femoral head viability, SUVmax and SUVmean were not significantly decreased in non-viable femoral heads compared to those in controls. Only the SUVmin was significantly reduced in non-viable femoral heads (mean ± standard deviation, 0.57 ± 0.38) than in controls (0.95 ± 0.26, p = 0.006) and contralateral femoral heads (1.36 ± 0.59, p = 0.008). The cutoff SUVmin of 0.61 (g/mL) yielded a sensitivity of 77.8% and specificity of 87.1% for detection of non-viable femoral heads (p = 0.006). Contralateral femoral necks of the femoral neck fracture patients showed significantly higher SUVmean and SUVmin (3.17 ± 1.20 and 1.64 ± 0.63) than those of controls (2.32 ± 0.53 and 1.04 ± 0.27; p = 0.021 and p = 0.002, respectively), which seemed to reflect weight bearing effect or metabolic derangement. CONCLUSIONS: The non-viable femoral heads from the femoral neck fracture showed significantly reduced SUVmin. Quantitative bone SPECT/CT holds promise for objective evaluation of femoral head viability.

Slit ventricle syndrome and early-onset secondary craniosynostosis in an infant.

PATIENT: Female, 14 months FINAL DIAGNOSIS: Slit ventricle syndrome Symptoms: Hydrocephalus • lethargy and seizure • vomiting MEDICATION: - Clinical Procedure: - Specialty: Pediatrics and Neonatology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: Shunt surgery is a common solution for hydrocephalus in infancy. Slit ventricle syndrome and secondary craniosynostosis are late-onset complications after shunt placement; these 2 conditions occasionally occur together. CASE REPORT: We report a case of early-onset secondary craniosynostosis with slit ventricle syndrome after shunt surgery in an infant, which led to a catastrophic increase in intracranial pressure (ICP). A 4-month-old girl with a Dandy-Walker malformation underwent a ventriculoperitoneal shunt procedure. Her head circumference (HC) gradually decreased to approximately the 5(th) percentile for her age group after shunt surgery. Seven months later, she developed increased ICP symptoms and underwent a shunt revision with a diagnosis of shunt malfunction. Her symptoms were temporarily relieved, but she repeatedly visited the emergency room (ER) for the same symptoms and finally collapsed, with an abrupt increase in ICP, 3 months later. Further evaluation revealed the emergence of sagittal synostosis at 7 months after initial shunt surgery. After reviewing all clinical data, slit ventricle syndrome combined with secondary craniosynostosis was diagnosed. Emergent cranial expansion surgery with shunt revision was performed, and the increased ICP signs subsided in the following days. CONCLUSIONS: Clinical suspicion and long-term HC monitoring are important in the diagnosis of slit ventricle syndrome and secondary craniosynostosis after shunt surgery, even in infants and young children.

Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells.

The stromal vascular fraction (SVF) in adipose tissue contains a pool of various stem and progenitor cells, but the existence of hematopoietic stem and progenitor cells (HSPCs) in the SVF has not been seriously considered. We detected the presence of HSPCs in the SVF by phenotypically probing with Lin(-)Sca-1(+)c-kit(+) (LSK) and functionally confirming the presence using colony-forming cell assay and assessing the long-term multilineage reconstitution ability after SVF transplantation. The LSK population in the SVF was 0.004% plus or minus 0.001%, and 5 x 10(5) freshly isolated SVF cells gave rise to 13 plus or minus 4 multilineage colonies. In addition, 0.15% plus or minus 0.03% of SVF cells was home to bone marrow (BM), especially near vascular and endosteal regions, 24 hours after blood transplantation. SVF transplantation was capable of generating a long-term (> 16 weeks), but variable extent (2.1%-32.1%) multilineage reconstitution in primary recipients, which was subsequently transferred to the secondary recipients by BM transplantation. All HSPCs within the SVF originated from the BM. Furthermore, the granulocyte-colony-stimulating factor (G-CSF) mobilization of HSPCs from BM markedly elevated the number of phenotypic and functional HSPCs in the SVF, which induced a high efficiency long-term reconstitution in multilineage hematopoiesis in vivo. Our results provide compelling evidence that adipose tissue is a novel extramedullary tissue possessing phenotypic and functional HSPCs.