Enhancing voxel-based dosimetry accuracy with an unsupervised deep learning approach for hybrid medical image registration.

BACKGROUND: Deformable registration is required to generate a time-integrated activity (TIA) map which is essential for voxel-based dosimetry. The conventional iterative registration algorithm using anatomical images (e.g., computed tomography (CT)) could result in registration errors in functional images (e.g., single photon emission computed tomography (SPECT) or positron emission tomography (PET)). Various deep learning-based registration tools have been proposed, but studies specifically focused on the registration of serial hybrid images were not found. PURPOSE: In this study, we introduce CoRX-NET, a novel unsupervised deep learning network designed for deformable registration of hybrid medical images. The CoRX-NET structure is based on the Swin-transformer (ST), allowing for the representation of complex spatial connections in images. Its self-attention mechanism aids in the effective exchange and integration of information across diverse image regions. To augment the amalgamation of SPECT and CT features, cross-stitch layers have been integrated into the network. METHODS: Two different 177 Lu DOTATATE SPECT/CT datasets were acquired at different medical centers. 22 sets from Seoul National University and 14 sets from Sunway Medical Centre are used for training/internal validation and external validation respectively. The CoRX-NET architecture builds upon the ST, enabling the modeling of intricate spatial relationships within images. To further enhance the fusion of SPECT and CT features, cross-stitch layers have been incorporated within the network. The network takes a pair of SPECT/CT images (e.g., fixed and moving images) and generates a deformed SPECT/CT image. The performance of the network was compared with Elastix and TransMorph using L1 loss and structural similarity index measure (SSIM) of CT, SSIM of normalized SPECT, and local normalized cross correlation (LNCC) of SPECT as metrics. The voxel-wise root mean square errors (RMSE) of TIA were compared among the different methods. RESULTS: The ablation study revealed that cross-stitch layers improved SPECT/CT registration performance. The cross-stitch layers notably enhance SSIM (internal validation: 0.9614 vs. 0.9653, external validation: 0.9159 vs. 0.9189) and LNCC of normalized SPECT images (internal validation: 0.7512 vs. 0.7670, external validation: 0.8027 vs. 0.8027). CoRX-NET with the cross-stitch layer achieved superior performance metrics compared to Elastix and TransMorph, except for CT SSIM in the external dataset. When qualitatively analyzed for both internal and external validation cases, CoRX-NET consistently demonstrated superior SPECT registration results. In addition, CoRX-NET accomplished SPECT/CT image registration in less than 6 s, whereas Elastix required approximately 50 s using the same PC's CPU. When employing CoRX-NET, it was observed that the voxel-wise RMSE values for TIA were approximately 27% lower for the kidney and 33% lower for the tumor, compared to when Elastix was used. CONCLUSION: This study represents a major advancement in achieving precise SPECT/CT registration using an unsupervised deep learning network. It outperforms conventional methods like Elastix and TransMorph, reducing uncertainties in TIA maps for more accurate dose assessments.

Utility of Lung Perfusion SPECT/CT in Detection of Pulmonary Thromboembolic Disease: Outcome Analysis.

Purpose: To evaluate the clinical outcome of Q-SPECT/CT in pulmonary thromboembolic disease. Methods: From Jan 2020 to Jan 2021, 30 consecutive patients (M:F = 8:22; median age = 52 year (21-89)) suspected of having acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension (CTEPH) were referred for non-contrasted Q-SPECT/CT. All patients were COVID-19 PCR negative. MSKCC Q-SPECT/CT and/or PISAPED criteria were used to determine the presence of thromboembolic disease in Q-SPECT/CT. Final diagnosis was made based on composite reference standards that included at least 2-month clinical cardiorespiratory assessment and follow-up imaging. Results: Q-SPECT/CT was positive in 19 patients: indeterminate in 1 and 10 were negative. Three false positive cases were observed during follow-up. Of the remaining 16 true positives, all patients' cardiorespiratory symptom were improved or stabilised after treatment with anticoagulants. The overall sensitivity, specificity, PPV, NPV and accuracy of Q-SPECT/CT were 100% (95% CI, 79.41-100%), 78.57% (95% CI, 49.20-95.34%), 84.21% (95% CI, 66.41-93.57%), 100% and 90.00% (95% CI, 73.47-97.89%) respectively. Conclusions: In the current COVID-19 pandemic, Q-SPECT/CT can be an alternative modality to detect pulmonary thromboembolic disease. Normal Q-SPECT/CT excludes pulmonary thromboembolic disease with high degree of certainty. However, false positive has been observed.

18 F-FDG PET-CT in Fitz-Hugh-Curtis Syndrome.

Positron emission tomography-computed tomography (PET-CT) has demonstrated its usefulness in evaluating nonspecific abdominal and inflammatory symptoms. We report a case of young woman with chronic right upper quadrant abdominal pain. Fluorine-18 fluorodeoxyglucose PET-CT showed subhepatic hypermetabolism. Subsequent diagnostic laparoscopy confirmed the uncommon diagnosis of Fitz-Hugh-Curtis syndrome.

Comparison of voxel S-value methods for personalized voxel-based dosimetry of 177 Lu-DOTATATE.

PURPOSE: Voxel-based dosimetry is potentially accurate than organ-based dosimetry because it considers the anatomical variations in each individual and the heterogeneous radioactivity distribution in each organ. Here, voxel-based dosimetry for 177 Lu-DOTATATE therapy was performed using single and multiple voxel S-value (VSV) methods and compared with Monte Carlo simulations. To verify these methods, we adopted sequential 177 Lu-DOTATATE single-photon emission computed tomography and X-ray computed tomography (SPECT/CT) dataset acquired from Sunway Medical Centre using the major vendor's SPECT/CT scanner (Siemens Symbia Intevo). METHODS: The administered activity of 177 Lu-DOTATATE was 7.99 ± 0.36 GBq. SPECT/CT images were acquired 0.5, 4, 24, and 48 h after injection in Sunway Medical Centre. For the multiple VSV method, VSV kernels of 177 Lu in media with various densities were generated by Geant4 Application for Emission Tomography (GATE) simulation first. The second step involved the convolution of the time-integrated activity map with each kernel to produce medium-specific dose maps. Third, each medium-specific dose map was masked using binary medium masks, which were generated from CT-based density maps. Finally, all masked dose maps were summed to generate the final dose map. VSV methods with four different VSV sets (1, 4, 10, and 20 VSVs) were compared. Voxel-wise density correction for the single VSV method was also performed. The absorbed doses in the kidneys, bone marrow, and tumors were analyzed, and the relative errors between the VSV and Monte Carlo simulation approaches were estimated. Organ-based dosimetry using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) was also compared. RESULTS: The accuracy of the multiple VSV approach increased with the number of dose kernels. The average dose estimation errors of a single VSV with density correction and 20 VSVs were less than 6% in most cases, although organ-based dosimetry using OLINDA/EXM yielded an error of up to 123%. The advantages of the single VSV method with density correction and the 20 VSVs over organ-based dosimetry were most evident in bone marrow and bone-metastatic tumors with heterogeneous medium properties. CONCLUSION: The single VSV method with density correction and multiple VSV method with 20 dose kernels enabled fast and accurate radiation dose estimation. Accordingly, voxel-based dosimetry methods can be useful for managing administration activity and for investigating tumor dose responses to further increase the therapeutic efficacy of 177 Lu-DOTATATE.

Extended Whole-body Ga-68 DOTATATE PET-CT in evaluating Tumour-Induced Osteomalacia: Case report and review of literature.

Tumour-induced osteomalacia is a rare paraneoplastic syndrome that manifests as chronic hypophosphataemia, non-specific bone pain and muscle weakness. It is generally caused by phosphaturic mesenchymal tumour (PMT), which is uncommonly associated with synchronous tumours. However, diagnosis is often delayed for several years due to the rarity, indolent growing nature and non-specific symptoms of the disease, often resulting in an overlook by clinicians during assessments. The patient initially presented with hypophosphataemia and generalised skeletal pain with multiple atraumatic fractures. Blood tests revealed serum calcium levels at the upper limit and extremely low inorganic phosphate levels. Herein, we report a case where two synchronous PMTs from two different sites were detected by 'extended' whole-body Ga-68 DOTATATE PET-CT, leading to remission of the disease after complete surgical removal. Early detection and diagnosis of PMT neoplasm is crucial, as complete surgical resection of this tumour is the only definitive treatment currently known. Upon excision, this curable disease will result in complete resolution of symptoms and blood parameters, leading to remission of the disease which significantly improves the patient's quality of life. PMT often over-expresses somatostatin receptors (SSTR), predominantly subtype 2A, and Ga-68 DOTATATE PET-CT is a selective SSTR imaging that targets this characteristic over-expression in these tumours. The high diagnostic accuracy of Ga-68 DOTATATE PET-CT should be the primary imaging modality for full evaluation of this disease.

Validity of Ultrasound Imaging in Measuring Quadriceps Muscle Thickness and Cross-Sectional Area in Patients Receiving Maintenance Hemodialysis.

BACKGROUND: Muscle wasting, prevalent in maintenance hemodialysis (HD) patients diagnosed with protein-energy wasting, represents an assessment challenge in the outpatient HD setting. Quadriceps muscle thickness (QMT) and cross-sectional area (CSA) assessment by ultrasound (US) is a potential surrogate measure for muscle wasting. We aimed to determine the validity of US to measure QMT and CSA against the gold standard-computed tomography (CT). METHODS: Twenty-six patients on HD underwent US and CT scans on the same day, postdialysis session. QMT for rectus femoris (RF) and vastus intermedius (VI) muscles was taken at the midpoint (MID) and two-thirds (2/3) of both thighs and CSA of the RF muscle (RFCSA ), respectively. Correlation between US and CT measurements was determined by intraclass correlation coefficient (ICC) and Bland-Altman plot. RESULTS: ICC (95% CI) computed between US and CT was 0.94 (0.87-0.97), 0.97 (0.93-0.99), 0.94 (0.87-0.97), 0.94 (0.86-0.97), and 0.92 (0.83-0.97) for RFMID, VIMID, RF2/3, VI2/3 , and RFCSA , respectively (all P < 0.001). Bland-Altman analysis indicated no bias in agreement between both methods. CONCLUSION: The US imaging offers a valid and quick bedside assessment approach to assess muscle wasting in HD patients.

68Ga-PSMA PET/CT and 18F-FDG PET/CT in Renal Cell Carcinoma.

Recent case reports and series have demonstrated the usefulness of Ga/F-PSMA PET/CT in restaging recurrent renal cancer after nephrectomy. We presented a case of a patient with renal mass who had undergone both F-FDG and Ga-PSMA PET/CT for diagnosis and staging. Concordant tracer uptake in the primary tumor and metastatic lesions was demonstrated by both radiotracers. Final histopathological reports revealed clear cell renal cell carcinoma. Furthermore, unusual left metacarpal bone metastasis was also detected.

Impact of 68Ga-DOTA-Peptide PET/CT on the Management of Gastrointestinal Neuroendocrine Tumour (GI-NET): Malaysian National Referral Centre Experience.

PURPOSE: The National Cancer Institute is the only referral centre in Malaysia that provides 68Ga-DOTA-peptide imaging. The purpose of this study is to determine the impact of 68Ga-DOTA-peptide PET/CT on the management of gastrointestinal neuroendocrine tumours (GI-NET). MATERIALS AND METHODS: A cross-sectional study was performed to review the impact of 68Ga-DOTA-peptide (68Ga-DOTATATE or 68Ga-DOTATOC) PET/CT on patients with biopsy-proven GI-NET between January 2011 and December 2015. Suspected NET was excluded. Demographic data, tumoral characteristics, change of disease stage, pre-PET intended management and post-PET management were evaluated. RESULTS: Over a 5-year period, 82 studies of 68Ga-DOTA-peptide PET/CT were performed on 44 GI-NET patients. The most common primary site was the rectum (50.0%) followed by the small bowel, stomach and colon. Using WHO 2010 grading, 40.9% of patients had low-grade (G1) tumour, 22.7% intermediate (G2) and 4.5% high (G3). Of ten patients scheduled for pre-operative staging, 68Ga-DOTA-peptide PET/CT only led to therapeutic change in three patients. Furthermore, false-negative results of 68Ga-DOTA-peptide PET/CT were reported in one patient after surgical confirmation. However, therapeutic changes were seen in 20/36 patients (55.6%) scheduled for post-surgical restaging or assessment of somatostatin analogue (SSA) eligibility. When 68Ga-DOTA-peptide PET/CT was used for monitoring disease progress during systemic treatment (sandostatin, chemotherapy, everolimus and PRRT) in metastatic disease, impact on management modification was seen in 19/36 patients (52.8%), of which 84.2% had inter-modality change (switch to everolimus, chemotherapy or PRRT) and 15.8% had intra-modality change (increased SSA dosage). CONCLUSIONS: 68Ga-DOTA-peptide PET/CT has a significant impact on management decisions in GI-NET patients as it can provide additional information on occult metastasis/equivocal lesions and supply the clinician an opportunity to select patients for targeted therapy.

18F-FDG Uptake in Benign Fibrous Histiocytoma of Adrenal Gland: A Potential Pitfall.

A 47-year-old man with newly diagnosed nasopharyngeal carcinoma underwent staging F-FDG PET/CT. Apart from showing increased FDG uptake in the primary site and locoregional nodal and liver metastases, an unusual site of intense FDG focus was demonstrated in the left adrenal gland. He underwent CT-guided biopsy, and the histopathologic diagnosis was benign fibrous histiocytoma.

Role of Pre-therapeutic (18)F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma.

OBJECTIVES: The present study aimed to evaluate the role of pre-therapeutic (18)fluorine-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) and maximum standardized uptake value (SUVmax) in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of the patients. METHODS: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy), who underwent pre-operative (18)F-FDG PET-CT staging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted (18)F-FDG PET-CT evaluations. The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan-Meier product-limit method. RESULTS: In a total of 40 patients, (18)F-FDG PET-CT scan led to changes in disease stage in 26 (65.0%) cases, with upstaging and downstaging reported in 10 (25.0%) and 16 (40.0%) patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the (18)F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0 (95% CI 3.0-5.0) months, whereas the median survival in the curative group has not been reached, based on the 12-month follow-up. Selection of treatment strategy on the basis of (18)F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03) and marginally significant at 12 months (P=0.03). On the basis of SUVmax, the relation between survival and SUVmax was not statistically significant. CONCLUSION: (18)F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre-treatment SUVmax failed to stablish its usefulness in the assessment of patient prognosis and survival outcome.

Erratum to: Diagnostic Performance of (68)Ga-DOTATATE PET/CT, (18)F-FDG PET/CT and (131)I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma.

[This corrects the article DOI: 10.1007/s13139-015-0339-z.].

Primary Squamous Cell Carcinoma of Trachea Arising 4 Years After Radioiodine Treatment of Papillary Carcinoma of Thyroid.

Primary squamous cell carcinoma (SCC) of the trachea is rare. Here, we presented a rare case of primary SCC of the trachea arising 4 years after radioiodine (RAI) treatment of papillary carcinoma of the thyroid. In this case, concomitant uptake of I-RAI and F-FDG was demonstrated in the thyroidal mass with tracheal invasion, which mimicked mixed well-differentiated and dedifferentiated thyroid carcinoma. The diagnosis of SCC of the trachea was made only after tracheal biopsy. This case illustrates that FDG-avid thyroid bed lesion, in the presence of thyroid carcinoma, may not necessarily be related to the thyroid pathology.

A Rare Case of Isolated Pericardial Effusion Detected by SPECT/CT on a Post-Therapeutic Radioiodine Whole-Body Scan.

We reported a rare finding of isolated pericardial uptake detected by SPECT/CT on posttherapeutic radioiodine whole body scan. This case highlights the usefulness of hybrid SPECT/CT, with subsequent correlation with biochemical results, in ruling out metastatic pericardial effusion in the postsurgical radioiodine remnant ablation setting. The effusion was resolved after reinstituted thyroid replacement therapy. Recombinant thyrotropin is recommended to avoid such rare but life-threatening complication.

Unusual Bone Superscan, MIBG Superscan, and 68Ga DOTATATE PET/CT in Metastatic Pheochromocytoma.

A 17-year-old adolescent boy with biochemically raised 2-hour urinary metanephrine and normetanephrine as well as CT findings of retroperitoneal soft tissue mass and bony metastases was referred for further assessment. Apart from Ga DOTATATE PET/CT evaluation, pretargeted systemic radionuclide therapy assessment with I-MIBG scintigraphy showed unusual phenomenon of MIBG superscan. Postsurgically, restaging Tc-MDP bone scintigraphy showed typical bone superscan features. The MIBG superscan was better delineated on post-I-MIBG therapy images.

Erratum to: Diagnostic Performance of (68)Ga-DOTATATE PET/CT, (18)F-FDG PET/CT and (131)I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma.

[This corrects the article DOI: 10.1007/s13139-015-0331-7.].

Diagnostic Performance of (68)Ga-DOTATATE PET/CT, (18)F-FDG PET/CT and (131)I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma.

PURPOSE: To evaluate the diagnostic performance of (68)Ga-DOTATATE (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT), (18)F-FDG PET/CT and (131)I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma. MATERIALS AND METHODS: Seventeen patients (male = 8, female = 9; age range, 13-68 years) with clinically proven or suspicious metastatic pheochromocytoma or paraganglioma were included in this prospective study. Twelve patients underwent all three modalities, whereas five patients underwent (68)Ga-DOTATATE and (131)I-MIBG without (18)F-FDG. A composite reference standard derived from anatomical and functional imaging findings, along with histopathological information, was used to validate the findings. Results were analysed on a per-patient and on per-lesion basis. Sensitivity and accuracy were assessed using McNemar's test. RESULTS: On a per-patient basis, 14/17 patients were detected in (68)Ga-DOTATATE, 7/17 patients in (131)I-MIBG, and 10/12 patients in (18)F-FDG. The sensitivity and accuracy of (68)Ga-DOTATATE, (131)I-MIBG and (18)F-FDG were (93.3 %, 94.1 %), (46.7 %, 52.9 %) and (90.9 %, 91.7 %) respectively. On a per-lesion basis, an overall of 472 positive lesions were detected; of which 432/472 were identified by (68)Ga-DOTATATE, 74/472 by (131)I-MIBG, and 154/300 (patient, n = 12) by (18)F-FDG. The sensitivity and accuracy of (68)Ga-DOTATATE, (131)I-MIBG and (18)F-FDG were (91.5 %, 92.6 % p < 0.0001), (15.7 %, 26.0 % p < 0.0001) and (51.3 %, 57.8 % p < 0.0001) respectively. Discordant lesions were demonstrated on (68)Ga-DOTATATE, (131)I-MIBG and (18)F-FDG. CONCLUSIONS: Ga-DOTATATE PET/CT shows high diagnostic accuracy than (131)I-MIBG scintigraphy and (18)F-FDG PET/ CT in mapping metastatic pheochromocytoma and paraganglioma.

False Negative (99m)Tc-Hydroxymethane Diphosphonate Three-phase Bone Scintigraphy and (99m)Tc-besilesomab Scan in Detecting Tibia Osteomyelitis Concomitant with Necrotizing Fasciitis.

We described a case of 51-year-old female patient presented with a right calf necrotising fasciitis (NF) where osteomyelitis (OM) was suspected. (99m)Tc-hydroxymethane diphosphonate three-phase bone scintigraphy and (99m)Tc-besilosomab scan failed to demonstrate classical features of OM. The final diagnosis was only made by isolating Acinetobacter sp. in both intra-operative bone and tissue cultures from below-knee amputation. As conclusions, the detection of lower limb OM by (99m)Tc-besilosomab scan is not easy when there is concurrence overlying NF. The unusual three-phase bone scan finding of pericortical accumulation of tracer as an early sign of OM is highlighted in this case.

Diagnostic Value of (68)Ga-DOTATATE PET/CT in Liver Metastases of Neuroendocrine Tumours of Unknown Origin.

PURPOSE: In neuroendocrine liver metastases of unknown primary, a multimodality approach is usually adopted and consists of transabdominal ultrasound, endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine techniques, endoscopy and exploratory surgery. The purpose of the study is to evaluate the diagnostic value of (68)Ga-DOTATATE positron emission tomography (PET)/CT as part of a multimodality approach in neuroendocrine liver metastases of unknown primary. MATERIALS AND METHODS: Six patients (M:F = 5:1, age range 28-56 years) with immunohistochemically proven neuroendocrine liver metastases but inconclusive initial CT work-up were retrospectively analysed. Clinical finding, histopathology, comparative imaging and follow-up were used to validate the results when ethically justified. RESULTS: (68)Ga-DOTATATE PET/CT identified the primary tumour in five out of six (83.3 %) patients: pancreas (n = 4) and stomach (n = 1). Out of three patients with indeterminate primary on initial CT, two patients were confirmed by (68)Ga-DOTATATE PET/CT. Absence of uptake in indeterminate primary of one patient was later confirmed negative by histopathology. In another three patients with undetected primary on initial CT, primary site was demonstrated in all patients with unsuspected metastases in two patients on (68)Ga-DOTATATE PET/ CT. No further work-up was done to confirm the primary in patients with distant metastases. Change of management was observed in three out of six (50 %) patients. CONCLUSION: Our small study indicates that (68)Ga-DOTATATE PET/CT is a promising diagnostic option in the multimodality approach to neuroendocrine liver metastases of unknown primary origin.

Dual thyroid ectopia with graves' disease: a case report and a review of the literature.

Ectopic thyroid or thyroid ectopia is a rare developmental anomaly with the prevalence of 1 per 100,000-300,000 population. Even rarer, such an anomaly manifests as dual thyroid ectopia. To our best knowledge, only one case has been reported on dual thyroid ectopia with Graves' disease in the English literature. We present here a case of dual thyroid ectopia complicated by Graves' disease, whereby the diagnosis was rendered through judicious use of various diagnostic modalities coupled with a close clinical follow-up. In this case, therapeutic consideration should be personalized with proper informed consent of the patient.