Diagnostic Value of Preoperative uPAR-PET/CT in Regional Lymph Node Staging of Oral and Oropharyngeal Squamous Cell Carcinoma: A Prospective Phase II Trial.

The detection of lymph node metastases is a major challenge in oral and oropharyngeal squamous cell carcinoma (OSCC and OPSCC). 68Ga-NOTA-AE105 is a novel positron emission tomography (PET) radioligand with high affinity to urokinase-type plasminogen activator receptor (uPAR), a receptor expressed on the surfaces of tumor cells. The aim of this study was to investigate the diagnostic value of uPAR-PET/CT (computerized tomography) in detecting regional metastatic disease in patients with OSCC and OPSCC compared to the current imaging work-up. In this phase II trial, patients with OSCC and OPSCC referred for surgical treatment were prospectively enrolled. Before surgery, 68Ga-NOTA-AE105 uPAR-PET/CT was conducted, and SUVmax values were obtained from the primary tumor and the suspected lymph nodes. Histology results from lymph nodes were used as the standard of truth of metastatic disease. The diagnostic values of 68Ga-uPAR-PET/CT were compared to conventional routine preoperative imaging results (CT and/or MRI). The uPAR expression in resected primary tumors and metastases was determined by immunohistochemistry and quantified digitally (H-score). A total of 61 patients underwent uPAR-PET/CT. Of the 25 patients with histologically verified lymph node metastases, uPAR-PET/CT correctly identified regional metastatic disease in 14 patients, with a median lymph node metastasis size of 14 mm (range 3-27 mm). A significant correlation was found between SUVmax and the product of the H-score and tumor depth (r = 0.67; p = 0.003). The sensitivity and specificity of uPAR-PET/CT in detecting regional metastatic disease were 56% and 100%, respectively. When added to CT/MRI, uPAR-PET was able to upstage 2/11 (18%) of patients with occult metastases and increase the sensitivity to 64%. The sensitivity and specificity of 68Ga-NOTA-AE105 uPAR-PET/CT were equivalent to those of CT/MRI. The significant correlation between SUVmax and uPAR expression verified the target specificity of 68Ga-NOTA-AE105. Despite the target specificity, the sensitivity of imaging is too low for nodal staging and it cannot replace neck dissection.

Prospective Phase II Trial of [68Ga]Ga-NODAGA-E[c(RGDyK)]2 PET/CT Imaging of Integrin αvß3 for Prognostication in Patients with Neuroendocrine Neoplasms.

Integrin αvß3, a subtype of the arginine-glycine-aspartate (RGD)-recognizing cell surface integrins, is upregulated on endothelial cells during angiogenesis and on tumor cells. Because of involvement in tumor growth, invasiveness and metastases, and angiogenesis, integrin αvß3 is an attractive target in cancers. In this study, we applied 68Ga-NODAGA-E[c(RGDyK)]2 for imaging of integrin αvß3 in patients with neuroendocrine neoplasms (NENs) and its potential use for prognostication. We hypothesized that 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT would show tumor lesion uptake and that higher tumor lesion uptake was associated with a poorer prognosis. Methods: Between December 2017 and November 2020 we prospectively enrolled 113 patients with NEN of all grades (2019 World Health Organization classification) for 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT. The scan was acquired 45 min after injection of 200 MBq of 68Ga-NODAGA-E[c(RGDyK)]2 Board-certified specialists in nuclear medicine and radiology analyzed the PET/CT measuring SUVmax in tumor lesions. Positive tumor lesions were defined as those with tumor-to-liver background ≥ 2. Maximal tumor SUVmax for each patient was used as a predictor of outcome. Patients were followed for at least 1 y to assess progression-free survival and overall survival. Results: Of 113 patients enrolled in the trial, 99 underwent 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT, with 97 patients having evaluable lesions. The patients predominantly had small intestinal (64%) or pancreatic (20%) NEN and most had metastatic disease (93%). Most patients had low-grade tumors (78%), whereas 22% had high-grade tumors. During a median follow-up of 31 mo (interquartile range, 26-38 mo), 62 patients (64%) experienced disease progression and 25 (26%) patients died. In total, 76% of patients had positive tumor lesions, and of the patients with high-grade tumors 91% had positive tumor lesions. High integrin αvß3 expression, defined as an SUVmax of at least 5.25, had a hazard ratio of 2.11 (95% CI, 1.18-3.78) and 6.95 (95% CI, 1.64-29.51) for progression-free survival and overall survival, respectively (P = 0.01 for both). Conclusion: Tumor lesion uptake of 68Ga-NODAGA-E[c(RGDyK)]2 was evident in patients with all grades of NEN. High uptake was associated with a poorer prognosis. Further studies are warranted to establish whether 68Ga-NODAGA-E[c(RGDyK)]2 PET/CT may become a prediction tool for identification of patients eligible for treatments targeting integrin αvß3.

Response Evaluation Following Radiation Therapy With 18F-FDG PET/CT: Common Variants of Radiation-Induced Changes and Potential Pitfalls.

Radiation therapy (RT) is one of the cornerstones in cancer treatment and approximately half of all patients will receive some form of RT during the course of their cancer management. Response evaluation after RT and follow-up imaging with 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) can be complicated by RT-induced acute, chronic or consequential effects. There is a general consensus that 18F-FDG PET/CT for response evaluation should be delayed for 12 weeks after completing RT to minimize the risk of false-positive findings. Radiation-induced late side effects in normal tissue can take years to develop and eventually cause symptoms that on imaging can potentially mimic recurrent disease. Imaging findings in radiation induced injuries depend on the normal tissue included in the irradiated volume and the radiation therapy regime including the total dose delivered, dose per fraction and treatment schedule. The intent for radiation therapy should be taken in consideration when evaluating the response on imaging, that is palliative vs curative or neoadjuvant vs adjuvant RT. Imaging findings can further be distorted by altered anatomy and sequelae following surgery within the radiation field. An awareness of common PET/CT-induced changes/injuries is essential when interpreting 18F-FDG PET/CT as well as obtaining a complete medical history, as patients are occasionally scanned for an unrelated cause to previously RT treated malignancy. In addition, secondary malignancies due to carcinogenic effects of radiation exposure in long-term cancer survivors should not be overlooked. 18F-FDG PET/CT can be very useful in response evaluation and follow-up in patients treated with RT, however, variants and pitfalls are common and it is important to remember that radiation-induced injury is often a diagnosis of exclusion.

T2-PROPELLER Compared to T2-FRFSE for Image Quality and Lesion Detection at Prostate MRI.

PURPOSE: The primary objective was to compare T2-FRFSE and T2-PROPELLER sequences for image quality. The secondary objective was to compare the ability to detect prostate lesions at MRI in the presence and absence of motion artefact using the 2 sequences. METHODS: 99 patients underwent 3 T MRI examination of the prostate, including T2-FRFSE and T2-PROPELLER sequences. All patients underwent prostate biopsy. Two independent readers rated overall image quality, presence of motion artefact, and blurring for both sequences using a 5-point Likert scale. Scores were compared for the whole group and for subgroups with and without significant motion artefact. Outcome for lesion detection at an MRI threshold of PI-RADS score ≥3 was compared between T2-FRFSE and T2-PROPELLER. RESULTS: The overall image quality was not significantly different between T2-FRFSE and T2-PROPELLER sequences (3.74 vs. 3.93, p = 0.275). T2-PROPELLER recorded a lesser degree of motion artefact (score 4.53 vs. 3.78, p <0.0001), but demonstrated greater image blurring (score 3.29 vs. 3.73, p <0.001). However, in a subgroup of patients with significant motion artefact on T2-FRFSE, the T2-PROPELLER sequence demonstrated significantly higher image quality (3.46 vs. 2.49, p <0.001). T2-FRFSE and T2-PROPELLER showed comparable positive predictive values for lesion detection at 93.2% and 97.7%, respectively. CONCLUSIONS: T2-PROPELLER provides higher quality imaging in the presence of motion artefact, but T2-FRFSE is preferred in the absence of motion. T2-PROPELLER is therefore recommended as a secondary T2 sequence when imaging requires repeat acquisition due to motion artefact.

Normal tolerance limits for side-to-side differences in diameters of major lower limbs arteries of 228 healthy subjects.

PURPOSE: To determine reference values and tolerance limits of between-side differences for the calibers of the common femoral artery (CFA), superficial femoral artery (SFA), popliteal artery (PA), dorsalis pedis artery (DPA), and posterior tibial artery (PTA). MATERIALS AND METHODS: Calibers of arteries, defined as the largest distance between internal hyperechogenic lines of the intima-media complex of the arterial wall, were measured during the diastole phase determined from echo-tracking B mode ultrasound scanning and grey-scale ultrasound in 228 healthy volunteers aged 18-81 years (43.1 ± 16.7). RESULTS: The mean, 95% confidence and tolerance limits covering 90% of population for left and right side of each artery were: CFA: 8.1 mm, 7.9-8.3 mm, 6.0-10.3 mm; 8.1 mm, 7.9-8.5 mm, 5.9-10.2 mm; SFA: 6.2 mm, 6.0-6.3 mm, 4.7-7.6 mm; 6.1 mm, 6.0-6.3 mm, 4.7-7.6 mm; PA: 6.1 mm, 6.0-6.2 mm, 4.6-7.6 mm; 6.1 mm, 5.9-6.2 mm, 4.5-7.6 mm; DPA: 2.0 mm, 1.9-2.0 mm, 1.2-2.7 mm; 2.0 mm, 1.9-2.0 mm, 1.2-2.8 mm; PTA: 2.1 mm, 2.0-2.1 mm, 1.4-2.8 mm; 2.1 mm, 2.1-2.2 mm, 1.4-2.8 mm, respectively. Tolerance limits for between-side differences and ratios were: CFA - 0.5-0.7 mm, 0.9-1.1; SFA - 0.5-0.6 mm, 0.9-1.1; PA - 0.5-0.5 mm, 0.9-1.1; DPA -0.4-0.4 mm, 0.8-1.2; PTA - 0.4-0.4 mm, 0.8-1.2. Regression analysis showed weight and age dependency of vessels diameters. There are no differences between men and woman in vessels size, except in DPA's, when body weight and age are taken into account in a regression analysis. CONCLUSIONS: We estimated normal reference tolerance limits of side-to-side differences in diameters of lower limb arteries. The limits can inform an investigator what differences in diameters occur in healthy individuals, and hence can serve as cut-offs in diagnostic and screening strategies.

Cross-sectional area of the femoral vein varies with leg position and distance from the inguinal ligament.

PURPOSE: The risk of complications associated with femoral venous catheterization could be potentially reduced if the procedure was performed at the location where the cross-sectional area (CSA) of the vessel is the largest. The diameter of the femoral vein depends on leg position as well as the distance from the inguinal ligament. We determined the CSA of the right femoral vein in three different leg positions at two distances from the inguinal ligament. SUBJECTS AND METHODS: Informed consent was given by 205 healthy volunteers aged 19-39 years, mean: 23±3 years (108 women, 97 men). Ultrasonographic examinations were performed using a linear 14-MHz transducer with CSA measurements in three leg positions: abduction, abduction+external rotation, abduction+external rotation+90° knee flexion/frog-leg position; at levels 20 mm caudally to the inguinal ligament, and 20 mm caudally to the inguinal crease. RESULTS: We found significant differences in mean values of CSA in three leg positions regardless of the measurement level. The largest mean CSA (114 mm2±35 mm2) was found at the proximal level in the frog-leg position. There was a significant association of the CSA with sex and height. The CSA in males was greater than in females in all leg positions at the level of 20 mm caudally to the inguinal crease, while 20 mm caudally to the inguinal ligament the CSA was larger in females. The CSA of 25% of the femoral vein was smaller than 45.0 mm2 at the proximal level, and 31.5 mm2 at the distal level, which refers to diameters of 5.3 mm, and 4.5 mm, respectively. CONCLUSIONS: The cross-sectional area of the femoral vein is the largest in the frog-leg position, and depends on gender.

Computerized tomography of the transverse pericardial sinus: Normal or pathologic?

The transverse pericardial sinus is a uniquely located structure subdivided into many parts. However, discrepancies still exist on the nomenclature and divisions. As noninvasive diagnostic technology such as CT and MR imaging improve, the transverse pericardial sinus and constituent recesses are visualized with more clarity, increasing the risk for misinterpretation. In this review, we will explore the anatomy of the transverse pericardial sinus and associated recesses with the goal of heightening awareness regarding the differential diagnosis between normal and pathological states as seen on CT. In addition, the inconsistencies of the right lateral superior aortic recess are also addressed. Last, we describe the clinical and surgical significance of the transverse pericardial sinus. Clin. Anat. 30:61-70, 2017. © 2016 Wiley Periodicals, Inc.

[Application of ultrasonography in central venous catheterization; access sites and procedure techniques]. / Aplicación de la ecografía en la cateterización venosa central; lugares de acceso y técnicas del procedimiento.

Central venous catheterization is commonly performed in clinical practice. Traditional procedural technique is based on anatomical landmarks, but is associated with a high risk of failure and complications. To decrease their incidence European and American societies recommend application of ultrasonography. Preliminary ultrasonographic examination allows for assessment of local anatomical relations as well as vessel morphology (diameter, patency), while real-time ultrasonography increases chances of successful needle insertion. This paper presents the most common venous access sites and procedure techniques.

Ultrasound assessment of the jugular and vertebral veins in healthy individuals: selected physiological aspects and morphological parameters.

AIM: Ultrasound assessment of morphological parameters of the internal jugular veins and vertebral veins in healthy individuals as well as their dependence on the patient's position. MATERIAL: The examinations were conducted in 185 healthy individuals (101 females and 84 males) aged 18-89. Ultrasound examinations were conducted with the use of a linear probe with the frequency of 5-9 MHz in the supine (0°) and sitting position (90°). RESULTS: In 154 cases (83.2%) on the left side and in 150 cases (81.1%) on the right side, the jugular veins were completely closed in the sitting position. In 31 cases (16.8%) on the left side and in 35 cases (18.9%) on the right side, they were merely narrowed. By contrast with the jugular veins, the cross-sectional area (CSA) of the vertebral veins was greater in the sitting position than in the supine position in a statistically significant way. The CSA values of the jugular veins in the supine position ranged from 0 cm(2) to 4.3 cm(2). There were no statistically significant differences in the CSA between men and women. The cross-sectional area of the right jugular vein in the supine position was greater in a statistically significant way than that of the left jugular vein. In this study population, the ratio of the cross-sectional areas of the jugular veins on both sides amounted to 8.5:1. CONCLUSIONS: The width of the jugular and vertebral veins significantly varies depending on the patient's position. The range of the CSA values for the jugular veins is broad, which should be taken into account when interpreting imaging findings. The internal jugular veins can show considerable asymmetry.

Internal jugular veins must be measured before catheterization.

STUDY OBJECTIVE: The study objective is to determine the cross-sectional area (CSA) of the right and left internal jugular vein (IJV) in supine position in healthy subjects. DESIGN: This is a prospective, nonrandomized study. SETTING: The setting is a university hospital. PATIENTS: The patients are 185 consenting healthy subjects. INTERVENTIONS: B-mode ultrasonography examinations of the right and left IJV were performed with the use of a linear 14-MHz transducer at the level of the cricoid cartilage. The CSA of the examined vessels was measured in a supine position. MEASUREMENTS AND MAIN RESULTS: The CSA on both sides differed by up to 850%. There were no statistically significant differences between CSA of IJVs in men and women. The CSA of the IJV on the right side was significantly greater than on the left side. The right IJV was more often classified as the "dominant" vessel (CSA being more than twice as large as the opposite side). A "small" vessel (CSA ≤ 0.4 cm(2)) was found in 54 cases (14.6%). In 9 subjects (4.9%), they were detected bilaterally. CONCLUSION: The CSA of IJVs varies widely. Although the CSA was found to be often greater on the right than on the left side, a "small" vessel may occur on both sides.

Ultrasound assessment of the caliber of the arteries in the lower extremities in healthy persons - the dependency on age, sex and morphological parameters of the subjects.

AIM: The aim of this paper was to evaluate the caliber of the following arteries in the lower extremities: the common femoral artery, superficial femoral artery, popliteal artery, posterior tibial artery and dorsalis pedis artery and to determine the relation of the calibers to age, sex and morphological parameters of the body such as weight, height and BMI of the subject. MATERIAL: Two hundred and twenty-eight healthy persons aged 18-81 were examined (average ±SD; 43.1±16.71): 134 women aged 19-74 (43.2±15.63) and 94 men aged 18-81 (43±18.22). METHODS: The study was conducted with the use of a linear probe of 7.5 MHz frequency. The vascular caliber was assessed after the color map (color Doppler) was placed on a B-mode image. RESULTS: The average and standard deviation values for the calibers of examined vessels were determined. The calibers of all vessels examined in the group of men were statistically significantly larger than those in the group of women. No statistically significant differences between the calibers of the right and left sides were determined. The statistically significant correlations were specified between the age and the caliber of the examined vessels; positive for large femoral arteries and negative for the arteries of the crus and foot. Positive, statistically significant correlations between the caliber and the height, weight and BMI were also reported. CONCLUSIONS: The reported calibers of the arteries in the lower extremities and their relation to age, sex and morphological parameters of the subjects enable the differentiation of the physiological remodeling of the vessels from the pathological processes in e.g. atherosclerosis or hypertension.