4D SPECT/CT: A Hybrid Approach to Primary Hyperparathyroidism.

Our rationale was to review the imaging options for patients with primary hyperparathyroidism and to advocate for judicious use of 4-dimensional (4D) SPECT/CT to visualize diseased parathyroid glands in patients with complex medical profiles or in whom other imaging modalities fail. We review the advantages and disadvantages of traditional imaging modalities used in preoperative assessment of patients with primary hyperparathyroidism: ultrasound, SPECT, and 4D CT. We describe a scheme for optimizing and individualizing preoperative imaging of patients with hyperfunctioning parathyroid glands using traditional modalities in tandem with 4D SPECT/CT. Using the input from radiologists, endocrinologists, and surgeons, we apply patient criteria such as large body habitus, concomitant multiglandular disease, multinodular thyroid disease, confusing previous imaging, and unsuccessful previous surgery to create an imaging paradigm that uses 4D SPECT/CT yet is cost-effective, accurate, and limits extraneous radiation exposure. 4D SPECT/CT capitalizes on the strengths of SPECT and 4D CT and addresses limitations that exist when these modalities are used in isolation. In select patients with complicated clinical parameters, preoperative imaging with 4D SPECT/CT can improve accuracy yet remain cost-effective.

Nasal epithelial cell culture fluorescence recovery after photobleaching predicts cystic fibrosis therapeutic response.

Background: Human nasal epithelial (HNE) cells can be sampled noninvasively and cultured to provide a model of the airway epithelium that reflects cystic fibrosis (CF) pathophysiology. We hypothesised that in vitro measures of HNE cell physiology would correlate directly with in vivo measures of lung physiology and therapeutic response, providing a framework for using HNE cells for therapeutic development and precision medicine. Methods: We sampled nasal cells from participants with CF (CF group, n=26), healthy controls (HC group, n=14) and single CF transmembrane conductance regulator (CFTR) mutation carrier parents of the CF group (CR group, n=16). Participants underwent lung physiology and sweat chloride testing, and nuclear imaging-based measurement of mucociliary clearance (MCC) and small-molecule absorption (ABS). CF participants completed a second imaging day that included hypertonic saline (HS) inhalation to assess therapeutic response in terms of MCC. HNE measurements included Ussing chamber electrophysiology, small-molecule and liquid absorption rates, and particle diffusion rates through the HNE airway surface liquid (ASL) measured using fluorescence recovery after photobleaching (FRAP). Results: Long FRAP diffusion times were associated with increased MCC response to HS in CF. This implies a strong relationship between inherent factors affecting ASL mucin concentration and therapeutic response to a hydrating therapy. MCC decreased with age in the CR group, which had a larger range of ages than the other two groups. Likely this indicates a general age-related effect that may be accentuated in this group. Measures of lung ABS correlated with sweat chloride in both the HC and CF groups, indicating that CFTR function drives this measure of paracellular small-molecule probe absorption. Conclusions: Our results demonstrate the utility of HNE cultures for assessing therapeutic response for hydrating therapies. In vitro measurements of FRAP were particularly useful for predicting response and for characterising important properties of ASL mucus that were ultimately reflected in lung physiology.

Mucociliary Clearance Differs in Mild Asthma by Levels of Type 2 Inflammation.

BACKGROUND: Although mucus plugging is a well-reported feature of asthma, whether asthma and type 2 inflammation affect mucociliary clearance (MCC) is unknown. RESEARCH QUESTION: Does type 2 inflammation influence mucus clearance rates in patients with mild asthma who are not receiving corticosteroids? STUDY DESIGN AND METHODS: The clearance rates of inhaled radiolabeled particles were compared between patients with mild asthma with low (n = 17) and high (n = 18) levels of T2 inflammation. Fraction exhaled nitric oxide (Feno) was used to prospectively segregate subjects into T2 Lo (Feno < 25 ppb) and T2 Hi (Feno > 35 ppb) cohorts. Bronchial brush samples were collected with fiber-optic bronchoscopy, and quantitative polymerase chain reaction was performed to measure expression of genes associated with T2 asthma. MCC rate comparisons were also made with a historical group of healthy control subjects (HCs, n = 12). RESULTS: The T2 Lo cohort demonstrated increased MCC when compared with both T2 Hi and historic HCs. MCC within the T2 Hi group varied significantly, with some subjects having low or zero clearance. MCC decreased with increasing expression of several markers of T2 airway inflammation (CCL26, NOS2, and POSTN) and with Feno. MUC5AC and FOXJ1 expression was similar between the T2Lo and T2Hi cohorts. INTERPRETATION: Increasing T2 inflammation was associated with decreasing MCC. High rates of MCC in T2 Lo subjects may indicate a compensatory mechanism present in mild disease but lost with high levels of inflammation. Future studies are required to better understand mechanisms and whether impairments in MCC in more severe asthma drive worse clinical outcomes.

Diagnostic Value of FDG PET/MRI in Females With Pelvic Malignancy-A Systematic Review of the Literature.

Hybrid imaging with F-18 fludeoxyglucose positron emission tomography/magnetic resonance imaging (FDG PET/MRI) has increasing clinical applications supplementing conventional ultrasound, CT, and MRI imaging as well as hybrid PET/CT imaging in assessing cervical, endometrial, and ovarian cancer. This article summarizes the existing literature and discusses the emerging role of hybrid PET/MRI in gynecologic malignancies. Thus, far, the published literature on the applications of FDG PET/MRI shows that it can have a significant impact on patient management by improving the staging of the cancers compared with PET/CT, influencing clinical decision and treatment strategy. For disease restaging, current literature indicates that PET/MRI performs equivalently to PET/CT. There appears to be a mild-moderate inverse correlation between standard-uptake-value (SUV) and apparent-diffusion-coefficient (ADC) values, which could be used to predict tumor grading and risk stratification. It remains to be seen as to whether multi-parametric PET/MRI imaging could prove valuable for prognostication and outcome. PET/MRI provides the opportunity for reduced radiation exposure, which is particularly relevant for a young female in need of multiple scans for treatment monitoring and follow-up. Fast acquisition protocols and optimized methods for attenuation correction are still evolving. Major limitations of PET/MRI remains such as suboptimal detection of small pulmonary nodules and lack of utility for radiation treatment planning, which pose an impediment in making PET/MRI a viable one-stop-shop imaging option to compete with PET/CT.

68Ga-DOTATATE PET/MRI for Neuroendocrine Tumors: A Pictorial Review.

Neuroendocrine tumors (NETs) constitute a variety of neoplastic entities and exhibit variable degrees of neuroendocrine differentiation and phenotypes, as well as genetic profiles. Ga-DOTATATE PET is a novel imaging technique for NET. Although PET/CT is commonly utilized for oncologic imaging, PET/MRI is particularly suited for NETs, as MRI provides greater soft tissue contrast than CT, allowing for improved detection and characterization of NETs, particularly when liver metastasis is suspected or needs to be ruled out. The current pictorial review aims to illustrate the complementary advantages, as well as pitfalls of Ga-DOTATATE PET/MRI in the evaluation of NETs.

Novel Findings on SPECT-CT Tc-99 Sestamibi Imaging for Primary Hyperparathyroidism.

BACKGROUND: The addition of SPECT-CT to Tc-99 sestamibi has become a valuable tool for parathyroid localization in primary hyperparathyroidism (PHP). However, the enhanced sensitivity of this test can lead to unexpected and significant findings. We sought to identify the frequency and types of nonparathyroid detections by SPECT-CT. MATERIALS AND METHODS: With institutional approval, we reviewed all SPECT-CT studies performed for PHP between October 2012 and August 2018 for incidental nonparathyroid abnormalities. The electronic medical record was referenced to determine the type of lesion confirmed by additional evaluation. RESULTS: Among 2413 studies, 652 patients (27%) had 677 (28%) nonparathyroid findings. The most common were thyroid nodules (331/677, 49%), including 47 (6.9%) malignancies to date: 40 papillary thyroid cancers (11 microcarcinomas), five follicular thyroid cancers, one medullary carcinoma, and one noninvasive follicular thyroid neoplasm with papillary-like features. One hundred and seventy-seven patients had pulmonary nodules (26%), of whom nine were diagnosed with primary lung lesions (6 non-small-cell cancers, one small-cell cancer, one carcinoid, and one pulmonary sequestration). SPECT-CT revealed 14 patients (2.1%) with breast abnormalities, including three cancers. Nine patients (1.3%) demonstrated metastatic diseases within the lungs (4), bones (3), and mediastinum (2). One patient was diagnosed with follicular lymphoma. Two intracranial tumors were also identified, as well as dysplastic Barrett's esophagitis (1), hiatal hernia (20, 3%), and aortic aneurysm (13, 1.8%). In all, 72/677 (10.6%) PHP patients exhibited premalignant or malignant nonparathyroid SPECT-CT findings. CONCLUSIONS: In patients undergoing localization for PHP with Tc-99 sestamibi SPECT-CT, nonparathyroid findings are frequent (27%) and can lead to newly diagnosed malignant or premalignant lesions in at least 3% of patients to date.

Differential 18F-FDG and 18F-Fluciclovine Uptake Pattern in a Patient With Poorly Differentiated Adenocarcinoma of the Lung and Prostate Cancer Biochemical Recurrence.

A 72-year-old man with a history of T1cN0M0 prostate adenocarcinoma and rising prostate-specific antigen underwent a fluciclovine PET/CT scan that showed high uptake in several para-aortic nodes, suspicious for prostate cancer. A right upper lobe single pulmonary nodule (SPN), demonstrated only mild uptake, which raised the suspicion for a lung primary. Subsequent FDG PET/CT showed high uptake in the SPN, revealing poorly differentiated adenocarcinoma at biopsy, but with no abnormal uptake in the para-aortic nodes. This case highlights the complementary potential of fluciclovine and FDG PET in patients with a history of prostate cancer biochemical recurrence and SPN.

Multiprobe Nuclear Imaging of the Cystic Fibrosis Lung as a Biomarker of Therapeutic Effect.

Background: Nuclear imaging biomarkers illustrate unique aspects of lung physiology and are useful for assessing therapeutic effects in cystic fibrosis (CF) lung disease. We have developed a multiprobe method to simultaneously measure mucociliary clearance (MCC) and paracellular absorption (ABS). MCC is a direct measure of mucus clearance. ABS has been related to airway surface liquid (ASL) absorption through previous in vitro studies. Methods: We describe baseline factors affecting MCC and ABS using data from a retrospective baseline group (n = 22) and the response of the measures to inhaled 7% hypertonic saline (HS) and dry powder mannitol using data from a prospective response group (n = 7). A retrospective healthy control group (n = 15) is also described. The baseline and control groups performed single measurements of MCC/ABS. The response group performed baseline measurements of MCC/ABS and measurements after each intervention. Results: ABS was correlated (Spearman's ρ = 0.51, p = 0.06) to sweat chloride, a systemic measure of cystic fibrosis transmembrane conductance regulator (CFTR) function, whereas MCC was not. Baseline MCC was depressed after Pseudomonas aeruginosa infection as we have previously described. MCC provided a more sensitive indication of therapeutic effect and indicated improved clearance with mannitol compared with HS. Conclusion: MCC provides a useful and well-established means of testing therapies directed at improving mucus clearance in the lung. ABS may provide a means of detecting local changes in ASL absorption and CFTR function in the lung. Both are useful tools for studying the key aspects of CF lung pathophysiology (ASL hyperabsorption and MCC depression) that link the basic genetic defects of CF to disease manifestations in the lung.

Complementary Molecular and Metabolic Characterization of Meningiomas With DOTATATE and FDG-PET: Advancing Treatment Planning and Prognostication.

Ga-DOTATATE imaging for meningiomas is gaining clinical use for selecting patients that may benefit from targeted therapy (eg, Lu-DOTATATE). We present an image of a 67-year-old man with an intracranial WHO grade III anaplastic meningioma. He underwent tumor resection followed by intensity-modulated radiation therapy but experienced a recurrence 25 months later. He received an F-(FDG) and Ga-DOTATATE PET/MR to evaluate for the presence of somatostatin receptor expression and guide subsequent treatment. The scans showed both concordant and discordant regions of uptake, indicating that high somatostatin receptor (SSTR2) expression may not coincide with areas of increased metabolic rate.

Sestamibi SPECT/CT versus SPECT only for preoperative localization in primary hyperparathyroidism: a single institution 8-year analysis.

BACKGROUND: Primary hyperparathyroidism is caused by single gland disease in 85% of cases and by multiglandular disease in 15%. Our aim was to discover if the addition of computed tomography acquisition/fusion on a hybrid scanner to traditional dual-phase single-photon emission tomography improves localization accuracy. METHODS: A prospective database was queried for the perioperative data of patients with sporadic primary hyperparathyroidism who had initial exploration from 2006-2014 with ≥6 month follow-up to define anatomy. Prior to 2010, patients had single-photon emission tomography (n = 633); after 2010, they had single-photon emission tomography/computed tomography (n= 755). RESULTS: In 1,388 patients, the rates of single gland disease (P=.8), bilateral exploration (P=.4), and negative imaging (145 patients, P=.33) were equal between imaging cohorts. In 1,186 patients with single gland disease, the positive predictive value of single-photon emission tomography/computed tomography was somewhat greater (90% vs 85%) and the accuracy of single-photon emission tomography/computed tomography was superior (83% vs 77%, P=.02). In the 202 patients with multiglandular disease, 20% had negative imaging results with no difference by type (single-photon emission tomography/computed tomography 17%, single-photon emission tomography 23%, P=.3), but single-photon emission tomography/computed tomography was more accurate (36%) than single-photon emission tomography (22%, P=.04) in predicting multiglandular disease. CONCLUSION: In a large cohort study of patients with sporadic primary hyperparathyroidism undergoing parathyroidectomy, positive single-photon emission tomography/computed tomography results provided more reliable operative guidance than single-photon emission tomography for both single gland disease and multiglandular disease.

Overnight delivery of hypertonic saline by nasal cannula aerosol for cystic fibrosis.

AIM: Inhaled hypertonic saline increases mucociliary clearance, improves pulmonary function, and decreases exacerbations in cystic fibrosis (CF) but contributes to the already significant treatment burden of CF. Overnight delivery of inhaled medications via a specially designed nasal cannula-aerosol device (Trans-nasal Pulmonary Aerosol Delivery [tPAD]) is an alternative approach. Here, we test whether overnight inhalation of hypertonic saline via tPAD improves mucociliary clearance and assess the tolerability of the device. METHOD: In this study, 12 CF subjects inhaled 7% hypertonic saline (HS) for 8 h overnight using the tPAD system. Safety and tolerability were assessed and measurements of mucociliary and absorptive clearance (MCC/ABS) were performed after the treatment. Comparisons were made versus sham treatment where the same subjects wore the nasal cannula overnight but did not receive aerosol. RESULTS: Both the HS and sham treatments were well-tolerated. Only one subject did not complete the overnight HS treatment. There were no significant differences in MCC associated with HS inhalation at any time point (90 min, 3 h, 6 h) in any lung zone. Changes in FEV1 on both study days were similar. There were no differences in quality of sleep between HS and sham nights as assessed with the modified Leeds Sleep Evaluation Questionnaire (mLSEQ). Sino-Nasal Outcome Test (SNOT-14) questionnaires demonstrated significant increases (worsening) in 2/14 symptom categories with HS. CONCLUSIONS: The most likely cause for the failure to accelerate MCC was under-dosing of HS relative to the active transport of salt from the airways.

Pediatric Brown Adipose Tissue on 18F-FDG PET: Diazepam Intervention.

Brown adipose tissue (BAT) has been widely reported to affect the efficacy of 18F-FDG PET in oncology. Several small studies have found that warming the patient both before 18F-FDG injection and during the uptake phase can reduce the frequency of BAT uptake. Pharmaceutical approaches such as propranolol and diazepam have also been used. Methods: We describe two case studies that demonstrated the impact of combined patient warming and diazepam administration on BAT uptake in pediatric 18F-FDG PET images. To support these findings, we performed a retrospective analysis of 139 patients: 71 who received warming only and 68 who received warming combined with diazepam. Results: BAT uptake was significantly less frequent in patients who received diazepam (16.2%) than in those who did not (33.8%) (P = 0.0167), particularly in female patients (7.4% vs. 26.7%) (P = 0.0486). Conclusion: Although patient warming alone reduces the frequency of BAT uptake, the addition of diazepam to patient warming significantly furthers the reduction in young patients, particularly female patients.

Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung.

Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult cystic fibrosis subjects. Experimental factors were assessed in 29 adult and paediatric cystic fibrosis subjects (51 scans). Patient factors were assessed in a subgroup with optimal aerosol deposition (37 scans; 24 subjects). Paediatric subjects (n=9) underwent initial and 2-year follow-up scans. Control subjects from a previously reported study are included for comparison.High rates of central aerosol deposition influenced measurements of ABS and, to a lesser extent, MCC. Depressed MCC in cystic fibrosis was only detectable in subjects with previous Pseudomonas aeruginosa infection. Cystic fibrosis subjects without P. aeruginosa had similar MCC to control subjects. Cystic fibrosis subjects had consistently higher ABS rates.We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in cystic fibrosis is associated with P. aeruginosa infection. ABS is consistently increased in cystic fibrosis.

Accuracy of early-phase versus dual-phase single-photon emission computed tomography/computed tomography in the localization of parathyroid disease.

OBJECTIVES/HYPOTHESIS: Preoperative localization for parathyroid disease has improved in recent years with the advent of dual-phase (99m) Tc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. However, dual-phase imaging is associated with increased cost, time, and radiation dose. The aim of this study was to investigate the need for late-phase imaging when using SPECT/CT for the preoperative localization of parathyroid disease. STUDY DESIGN: Retrospective chart analysis. METHODS: A retrospective review of 75 patients who underwent preoperative imaging localization and subsequent surgical resection for parathyroid disease at a tertiary referral center was performed. Of these, 50 patients met study criteria including preoperative SPECT/CT imaging and specific reporting of early- and late-phase focal radiotracer uptake. Localization accuracy was verified with definitive surgical findings confirmed by histological analysis and evidence of biochemical cure. RESULTS: Accurate localization of adenoma(s) was seen in 78.0% of patients using dual-phase SPECT/CT. Early-phase imaging alone localized 76.0%, whereas late-phase imaging alone localized 74.0%. Sensitivity and specificity for dual-phase imaging was 84.8% and 89.6%, respectively. In comparison, early-phase localization alone was found to have a sensitivity/specificity of 84.4%/89.4%; sensitivity/specificity of late-phase scanning alone was found to be 80.4%/89.1%. Dual-phase SPECT/CT scanning did not provide a statistically significant improvement in adenoma localization when compared to early-phase scanning alone. CONCLUSIONS: Although further investigation is needed, the results of this study suggest that early-phase SPECT/CT scanning alone may obviate the need for dual-phase SPECT/CT scanning in the initial preoperative localization workup of parathyroid disease. LEVEL OF EVIDENCE: 4.

(99m)Tc MIBI SPECT findings in parathyromatosis--a rare entity causing recurrent hyperparathyroidism.

Parathyromatosis is a rare clinical condition resulting in recurrent hyperparathyroidism that often poses challenges in its diagnosis and complete surgical cure. We report the (99m)Tc MIBI SPECT findings in a patient with recurrent hyperparathyroidism requiring multiple parathyroid explorations. MIBI SPECT helped localize the areas of these "recurrent parathyroid lesions" that were often found outside of the expected locations within the neck.

Left ventricular myocardium metastasis in a patient with primary renal cell carcinoma detected by 18F-FDG PET/CT.

Cardiac metastases from renal cell carcinoma are rare but should be recognized when present. We report PET/CT findings in a patient with headache and diplopia and cerebral metastasis from an unknown primary of clear cell adenocarcinoma origin. PET/CT revealed uptake with a left renal cell carcinoma, and revealed multiple metastatic lesions, including an FDG-avid metastasis within the left ventricular myocardium.

Cecal volvulus associated with intestinal malrotation presenting as postoperative intestinal obstruction.

OBJECTIVE: To report a case of intestinal malrotation predisposing to cecal volvulus following nonabdominal surgery in an adult. PRESENTATION AND INTERVENTION: A 23-year-old male with known anorectal malformation developed a postoperative intestinal obstruction following percutaneous nephrolithotomy for left renal calculus. Computed tomography of the abdomen revealed a grossly dilated cecum (9 cm) with ileocecal junction on the left side and small bowel loops on the right side of the abdomen. The patient underwent emergency exploratory laparotomy and retroperitonealization cecopexy. Bowel functions were normal at the follow-ups. CONCLUSION: This case highlights the importance of suspecting cecal volvulus even following nonabdominal surgery in the presence of predisposing factors.

Improved Benefit of SPECT/CT Compared to SPECT Alone for the Accurate Localization of Endocrine and Neuroendocrine Tumors.

OBJECTIVE: To assess the clinical utility of SPECT/ CT in subjects with endocrine and neuroendocrine tumors compared to SPECT alone. MATERIAL AND METHODS: 48 subjects (31 women;17 men; mean age 54±11) with clinical suspicion or diagnosis of endocrine and neuroendocrine tumor had 50 SPECT/CT scans (32 Tc-99m MIBI, 5 post treatment I-131, 8 In-111 Pentetreotide, and 5 I-123 MIBG). SPECT alone findings were compared to SPECT/CT and to pathology or radiological follow up. RESULTS: From the 32 Tc-99m MIBI scans, SPECT accurately localized the lesion in 22 positive subjects while SPECT/CT did in 31 subjects. Parathyroid lesions not seen on SPECT alone were smaller than 10 mm. In five post treatment I-131 scans, SPECT alone neither characterized, nor localized any lesions accurately. SPECT/CT revealed 3 benign etiologies, a metastatic lymph node, and one equivocal lesion. In 8 In-111 Pentetreotide scans, SPECT alone could not localize primary or metastatic lesions in 6 subjects all of which were localized with SPECT/CT. In five I-123 MIBG scans, SPECT alone could not detect a 1.1 cm adrenal lesion or correctly characterize normal physiologic adrenal uptake in consecutive scans of the same patient with prior history of adrenelectomy, all of which were correctly localized and characterized with SPECT/CT. CONCLUSION: SPECT/CT is superior to SPECT alone in the assessment of endocrine and neuroendocrine tumors. It is better in lesion localization and lesion characterization leading to a decrease in the number of equivocal findings. SPECT/CT should be included in the clinical work up of all patients with diagnosis or suspicion of endocrine and neuroendocrine tumors. CONFLICT OF INTEREST: None declared.