Radiological features and metastatic patterns of thymic neuroendocrine tumours.

AIM: To investigate the clinical and image features of thymic neuroendocrine tumours (NETs), and characterise the radiological patterns of recurrence and metastasis on serial imaging studies. MATERIALS AND METHODS: The study included 14 patients (11 males) with a histopathological diagnosis of thymic NETs (one typical carcinoid, eight atypical carcinoid, and five large cell neuroendocrine carcinoma). Preoperative images were assessed for features of primary tumours. Follow-up imaging studies were evaluated for the patterns of metastasis or recurrence. RESULTS: Underlying endocrine or autoimmune disorders were present in four patients (29%), including multiple endocrine neoplasia (MEN) type 1 (n=3) and autoimmune thyroiditis (n=1). On preoperative imaging, the primary tumours were commonly lobulate and heterogeneous, infiltrated the surrounding fat, and showed ≥50% abutment of the mediastinal structures, with the mean longest diameter of 14 cm (range: 4.1-28 cm). No significant differences of preoperative imaging features were noted among histopathological subtypes. Metastasis or recurrence was noted in 11 of the 14 patients (79%). Ten patients developed intrathoracic metastasis or recurrence, involving thoracic lymph nodes (n=7), pleura (n=4), lung (n=4), pericardium (n=4), and local recurrence in the postoperative mediastinum (n=3). Eight of the 11 patients also had extra-thoracic metastasis, involving bone (n=6), abdominal lymph nodes (n=4), liver, pancreas, kidney, adrenal gland, spleen and brain (n=1 for each site). CONCLUSIONS: Thymic NETs presented as a large, lobulate, heterogeneous mass with an infiltrative nature. Metastasis and recurrence were frequent, most commonly involving thoracic lymph nodes, while extra-thoracic metastasis to bones and abdominal lymph nodes were also noted.

Patterns of metastasis and recurrence in thymic epithelial tumours: longitudinal imaging review in correlation with histological subtypes.

AIM: To determine the patterns of metastasis and recurrence in thymic epithelial tumours based on longitudinal imaging studies, and to correlate the patterns with World Health Organization (WHO) histological classifications. MATERIALS AND METHODS: Seventy-seven patients with histopathologically confirmed thymomas (n=62) and thymic carcinomas (n=15) who were followed with cross-sectional follow-up imaging after surgery were retrospectively studied. All cross-sectional imaging studies during the disease course were reviewed to identify metastasis or recurrence. The sites of involvement and the time of involvement measured from surgery were recorded. RESULTS: Metastasis or recurrence was noted in 24 (31%) of the 77 patients. Patients with metastasis or recurrence were significantly younger than those without (median age: 46 versus 60, respectively; p=0.0005), and more commonly had thymic carcinomas than thymomas (p=0.002). The most common site of involvement was the pleura (17/24), followed by the lung (9/24), and thoracic nodes (9/24). Abdominopelvic involvement was noted in 12 patients, most frequently in the liver (n=8). Lung metastasis was more common in thymic carcinomas than thymomas (p=0.0005). Time from surgery to the development of metastasis or recurrence was shortest in thymic carcinoma, followed by high-risk thymomas, and was longest in low-risk thymoma (median time in months: 25.1, 68.8, and not reached, respectively; p=0.0015). CONCLUSIONS: The patterns of metastasis and recurrence of thymic epithelial tumours differ significantly across histological subgroups, with thymic carcinomas more commonly having metastasis with shorter length of time after surgery. The knowledge of different patterns of tumour spread may contribute to further understanding of the biological and clinical behaviours of these tumours.

Intrathymic cyst: clinical and radiological features in surgically resected cases.

AIM: To investigate radiological and clinical characteristics of pathologically proven cases of intrathymic cysts. MATERIALS AND METHODS: The study population consisted of 18 patients (five males, 13 females; median age 56 years) with pathologically confirmed intrathymic cysts who underwent thymectomy and had preoperative chest computed tomography (CT) available for review. The patient demographics, clinical presentation, and preoperative radiological diagnoses were reviewed. CT images were evaluated for shape, contour, location of the cysts and the presence of adjacent thymic tissue, mass effect, calcifications, and septa. The size and CT attenuations of the cysts were measured. RESULTS: The most common CT features of intrathymic cysts included oval shape (9/18; 50%), smooth contour (12/18; 67%), midline location (11/18; 61%), the absence of visible adjacent thymic tissue (12/18; 67%), and the absence of calcification (16/18; 89%). The mean longest diameter and the longest perpendicular diameter were 25 mm (range 17-49 mm) and 19 mm (range 10-44 mm), respectively. The mean CT attenuation was 38 HU (range 6-62 HU) on contrast-enhanced CT, and was 45 HU (range 26-64 HU) on unenhanced CT (p = 0.41). The CT attenuation was >20 HU in 15 of 18 patients (83%). Preoperative radiological diagnosis included thymoma in 11 patients. CONCLUSION: In surgically removed, pathologically proven cases of intrathymic cyst, the CT attenuation was >20 HU in most cases, leading to the preoperative diagnosis of thymoma. Awareness of the spectrum of imaging findings of the entity is essential to improve the diagnostic accuracy and patient management.

Revisiting the relationship between tumour volume and diameter in advanced NSCLC patients: An exercise to maximize the utility of each measure to assess response to therapy.

AIM: To revisit the presumed relationship between tumour diameter and volume in advanced non-small-cell lung cancer (NSCLC) patients, and determine whether the measured volume using volume-analysis software and its proportional changes during therapy matches with the calculated volume obtained from the presumed relationship and results in concordant response assessment. MATERIALS AND METHODS: Twenty-three patients with stage IIIB/IV NSCLC with a total of 53 measurable lung lesions, treated in a phase II trial of erlotinib, were studied with institutional review board approval. Tumour volume and diameter were measured at baseline and at the first follow-up computed tomography (CT) examination using volume-analysis software. Using the measured diameter (2r) and the equation, calculated volume was obtained as (4/3)πr(3) at baseline and at the follow-up. Percent volume change was obtained by comparing to baseline for measured and calculated volumes, and response assessment was assigned. RESULTS: The measured volume was significantly smaller than the calculated volume at baseline (median 11,488.9 mm(3) versus 17,148.6 mm(3); p < 0.0001), with a concordance correlation coefficient (CCC) of 0.7022. At follow-up, the measured volume was once again significantly smaller than the calculated volume (median 6573.5 mm(3) versus 9198.1 mm(3); p = 0.0022), with a CCC of 0.7408. Response assessment by calculated versus measured volume changes had only moderate agreement (weighted κ = 0.545), with discordant assessment results in 20% (8/40) of lesions. CONCLUSION: Calculated volume based on the presumed relationship significantly differed from the measured volume in advanced NSCLC patients, with only moderate concordance in response assessment, indicating the limitations of presumed relationship.

Assessing clinical utility of machine learning and artificial intelligence approaches to analyze speech recordings in multiple sclerosis: A pilot study.

BACKGROUND: An early diagnosis together with an accurate disease progression monitoring of multiple sclerosis is an important component of successful disease management. Prior studies have established that multiple sclerosis is correlated with speech discrepancies. Early research using objective acoustic measurements has discovered measurable dysarthria. METHOD: The objective was to determine the potential clinical utility of machine learning and deep learning/AI approaches for the aiding of diagnosis, biomarker extraction and progression monitoring of multiple sclerosis using speech recordings. A corpus of 65 MS-positive and 66 healthy individuals reading the same text aloud was used for targeted acoustic feature extraction utilizing automatic phoneme segmentation. A series of binary classification models was trained, tuned, and evaluated regarding their Accuracy and area-under-the-curve. RESULTS: The Random Forest model performed best, achieving an Accuracy of 0.82 on the validation dataset and an area-under-the-curve of 0.76 across 5 k-fold cycles on the training dataset. 5 out of 7 acoustic features were statistically significant. CONCLUSION: Machine learning and artificial intelligence in automatic analyses of voice recordings for aiding multiple sclerosis diagnosis and progression tracking seems promising. Further clinical validation of these methods and their mapping onto multiple sclerosis progression is needed, as well as a validating utility for English-speaking populations.

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging.

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.

Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.

UNLABELLED: ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE. BACKGROUND: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. METHODS: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed. RESULTS: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4). CONCLUSION: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Inhibition of thyrotropin-stimulated iodide uptake in FRTL-5 thyroid cells by crude immunoglobulin fractions from patients with goitrous and atrophic autoimmune thyroiditis.

We studied the effects of crude immunoglobulin (Ig) fractions of serum from patients with goitrous and atrophic autoimmune thyroiditis on TSH-, thyroid-stimulating immunoglobulin (TSI)-, forskolin-, and dibutyryl cAMP-stimulated 125I uptake by FRTL-5 thyroid cells. TSH-stimulated 125I uptake was inhibited by the Ig fractions from 15 patients with atrophic thyroiditis who had serum TSH binding inhibitor Igs (TBII), 10 (62.5%) of 16 TBII-negative patients with atrophic thyroiditis, 7 (43.8%) of 16 hypothyroid patients with goitrous thyroiditis who had no TBII activity, and only 2 (15.4%) of 13 euthyroid patients with goitrous thyroiditis who were negative for TBII. The mean inhibition of TSH-stimulated 125I uptake produced by the crude Igs from the former 3 groups of hypothyroid patients was statistically significant (P less than 0.001, P less than 0.001, and P less than 0.01, respectively) and correlated closely with the ability of the Ig fractions to inhibit TSI-stimulated 125I uptake (r = 0.882) and TSH-stimulated cAMP accumulation (r = 0.929). The inhibition of TSH- or TSI-stimulated 125I uptake by Ig samples containing TBII correlated significantly with the TBII activities. On the other hand, in the presence of Igs from TBII-negative hypothyroid patients, the inhibition of TSH-stimulated 125I uptake correlated significantly with that of forskolin-stimulated 125I uptake (r = 0.685). Although 6 (12.8%) of 47 Ig samples from hypothyroid patients inhibited dibutyryl cAMP-stimulated 125I uptake, the activities were marginal. These findings suggest that at least 2 types of antibodies are involved in the inhibition of TSH- or TSI-stimulated 125I uptake: 1 being a competitive inhibitor of TSH binding to its receptors, and another exerting influence on a step subsequent to TSH or TSI binding, presumably through adenylate cyclase inhibition.

Role of thyrotropin receptor antibodies in the development of hyperthyroidism: follow-up studies on nine patients with Graves' disease.

TSH binding inhibitor immunoglobulin (TBII) and thyroid-stimulating antibody (TSAb) activities were measured serially for 4-32 months in nine patients before and during development of hyperthyroidism due to Graves' disease. Initially, all were euthyroid, seven had thyroid enlargement, one had proptosis, and seven had high serum titers of antithyroid microsomal antibodies. The occurrence of hyperthyroidism was preceded by detection of both TBII and TSAb in four patients and detection of TSAb alone in four patients. One patient had neither TBII nor TSAb when euthyroid. The mean initial TBII and TSAb activities were 10.2 +/- 15.2% (+/- SD) and 2677 +/- 4620%, respectively, when these patients were euthyroid. When they became hyperthyroid, both TBII and TSAb activities increased in all patients. At that time, TBII was detected in all but one (eight of nine subjects; 88.9%), with a mean activity of 58.8 +/- 23.4% (+/- SD), and TSAb was detected in all nine patients, with a mean value of 4508 +/- 4429%. These findings not only indicate the crucial role of TSH receptor antibodies in the development of hyperthyroidism due to Graves' disease, but also suggest that a certain period of subclinical Graves' disease exists before the onset of overt hyperthyroidism in most patients, in the sense that they have TSH receptor antibodies, especially TSAb, in their serum even though they are euthyroid.

Follow-up study of postoperative patients with thyroid cancer by thallium-201 scintigraphy and serum thyroglobulin measurement.

The utility of 201TI scintigraphy and thyroglobulin measurement in the follow-up observation of postoperative patients with thyroid cancer was evaluated. Thallium-201 scintigraphy was performed in 149 postoperative patients with thyroid cancer. Serum thyroglobulin concentration was concomitantly evaluated in 86 patients. Among 55 patients with positive 201TI scans, 51 patients (92.7%) had recurrent diseases, while 80 of 94 patients (85.1%) with negative scans were free of disease. Twenty-five of 28 patients (89.3%) with elevated thyroglobulin levels were recurrent and 43 of 58 patients (74.1%) with normal thyroglobulin level had no recurrence nor metastasis. All 19 patients with positive 201TI scans and elevated thyroglobulin level had recurrent lesions. Seven of 10 patients with negative 201TI scans and elevated thyroglobulin level showed the presence of metastasis. By concomitant measurement of serum thyroglobulin, more than half of the recurrent patients with negative 201TI scintigraphy were detected. Both 201TI scintigraphy and serum thyroglobulin measurement should be undertaken in the follow-up evaluation of postoperative patients with thyroid cancer.

Magnetic resonance imaging of the thorax. Past, present, and future.

Magnetic resonance imaging is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

Magnetic resonance imaging of the thorax. Past, present, and future.

Magnetic resonance is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

Magnetic resonance T2* measurements of the normal human lung in vivo with ultra-short echo times.

The objective of this study was to measure T2* values of the normal human lung in vivo during breathhold using a rapid gradient-echo sequence with ultra-short echo times (TE). A sagittal slice of the right lung was imaged in six volunteers with various TE ranging from 0.5 ms to 5 ms using a clinical 1.5 Tesla MR scanner. T2* values were calculated in a region of interest in the dependent and non-dependent lung. In the dependent lung, T2* values of 1.1 ms+/-0.15 ms were measured, and in the non-dependent lung, 0.86 ms+/-0.11 (p < 0.01). T2* measurements of the normal human lung during breathhold are feasible with a clinical MR unit. The short T2* values require the use of very short TE times (< 2.5 ms) in gradient-echo sequences to obtain adequate signal intensity from lung tissue.

Lymphoproliferative disorders of the thyroid gland: radiological appearances.

Images of lymphoproliferative disorders of the thyroid by ultrasonography (US), computed tomography (CT), 99Tcm and 67Ga scintigraphy were analysed in eight patients (two men and six women, aged 42-83 years). Seven patients were diagnosed as having primary lymphoma and one plasmacytoma. Ultrasound revealed a solid mass with homogeneous and very low echogenicity clearly distinguishable from residual thyroid tissue in five patients, diffuse hypoechoic goitre in one and multiple irregular hypoechoic nodules in both lobes in the patient with plasmacytoma (Case 8). Computed tomography demonstrated a focal low-density area in six cases of lymphoma and decreased density throughout the gland in the other two patients. 99Tcm scintigraphy showed hemilobar enlargement with decreased and uneven trapping, cold area or complete lobar defect in six patients with lymphoma and no trapping in the case of plasmacytoma. 67Ga scintigraphy demonstrated high accumulation in lymphoma and faint accumulation in the case of plasmacytoma. Radiological manifestations with a focal lesion were considered typical and diagnostic of primary thyroid lymphoma, while in one case with diffuse infiltration through the whole gland, the differential diagnosis from Hashimoto's thyroiditis could not be made. In the final case, cells infiltrated diffusely to form islands with patchy distribution among well preserved follicles, correlating with the multiple hypoechoic areas observed by US.

Assessment of pulmonary perfusion using a subtracted HASTE image between diastole and systole.

The MR signal intensity change in the pulmonary parenchyma during the cardiac cycle was studied using HASTE sequence in volunteers. In addition, the potential to assess pulmonary perfusion abnormality by subtraction between diastolic and systolic HASTE images was tested in a pig model of pulmonary embolism. Signal intensity decreased in systole while it increased gradually in diastole. In a pig model with pulmonary embolism, subtracted images could identify the perfusion abnormality. Thus, subtraction of diastolic and systolic HASTE images has the potential to detect pulmonary perfusion abnormality. The technique may provide a new simple method for evaluating pulmonary perfusion.

Oxygen-enhanced magnetic resonance ventilation imaging of lung.

The oxygen-enhanced magnetic resonance (MR) ventilation imaging is a new technique, and the full extent of its physiological significance has not been elucidated. This review article includes background on (1) respiratory physiology; (2) mechanism and optimization of oxygen-enhanced MR imaging technique; (3) recent applications in animal and human models; and (4) merits and demerits of the technique in comparison with hyperpolarized noble gas MR ventilation imaging. Application of oxygen-enhanced MR ventilation imaging to patients with pulmonary diseases has been very limited. However, we believe that further basic studies, as well as clinical applications of this new technique will define the real significance of oxygen-enhanced MR ventilation imaging in the future of pulmonary functional imaging and its usefulness for diagnostic radiology.

Quantification of pulmonary perfusion with MR imaging: recent advances.

Recent advances in magnetic resonance pulmonary perfusion imaging are reviewed, focusing on magnetic resonance perfusion imaging using gadolinium contrasts agents or spin labeling of blood using naturally flowing spins as the source of intravascular signal. These recent developments in magnetic resonance imaging have made it possible to analyze data quantitatively which holds significant potential for clinical imaging of lung perfusion and opens windows to functional MR imaging of the lung. We believe that fast magnetic resonance functional imaging will play an important role in the assessment of pulmonary function and the pulmonary disease process.

Fast magnetic resonance imaging techniques.

This article reviews fast magnetic resonance (MR) techniques currently used for body imaging. Improvements in gradient performance have made very short repetition and echo times on clinical scanners feasible, thus enabling subsecond image acquisition. The article provides a fundamental overview of the technical aspects from the concept of k-space and k-space segmentation technique, fast MR imaging techniques including fast spin echo, fast gradient echo with or without magnetization preparation to echo planar and hybrid techniques. The article also addresses the use of different fat suppression techniques in MR imaging of the body and improvements in coil technology to obtain faster images and higher signal-to-noise.

Fast magnetic resonance imaging of the lung.

The impact of fast MR techniques developed for MR imaging of the lung will soon be recognized as equivalent to the high-resolution technique in chest CT imaging. In this article, the difficulties in MR imaging posed by lung morphology and its physiological motion are briefly introduced. Then, fast MR imaging techniques to overcome the problems of lung imaging and recent applications of the fast MR techniques including pulmonary perfusion and ventilation imaging are discussed. Fast MR imaging opens a new exciting window to multi-functional MR imaging of the lung. We believe that fast MR functional imaging will play an important role in the assessment of pulmonary function and disease process.

T2* and proton density measurement of normal human lung parenchyma using submillisecond echo time gradient echo magnetic resonance imaging.

OBJECTIVE: To obtain T2* and proton density measurements of normal human lung parenchyma in vivo using submillisecond echo time (TE) gradient echo (GRE) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Six normal volunteers were scanned using a 1.5-T system equipped with a prototype enhanced gradient (GE Signa, Waukausha, WI). Images were obtained during breath-holding with acquisition times of 7-16 s. Multiple TEs ranging from 0.7 to 2.5 ms were tested. Linear regression was performed on the logarithmic plots of signal intensity versus TE, yielding measurements of T2* and proton density relative to chest wall muscle. Measurements in supine and prone position were compared, and effects of the level of lung inflation on lung signal were also evaluated. RESULTS: The signal from the lung parenchyma diminished exponentially with prolongation of TE. The measured T2* in six normal volunteers ranged from 0.89 to 2.18 ms (1.43 +/- 0.41 ms, mean +/- S.D.). The measured relative proton density values ranged between 0.21 and 0.45 (0.29 +/- 0.08, mean +/- S.D.). Calculated T2* values of 1.46 +/- 0.50, 1.01 +/- 0.29 and 1.52 +/- 0.18 ms, and calculated relative proton densities of 0.20 +/- 0.03, 0.32 +/- 0.13 and 0.35 +/- 0.10 were obtained from the anterior, middle and posterior portions of the supine right lung, respectively. The anterior-posterior proton density gradient was reversed in the prone position. There was a pronounced increase in signal from lung parenchyma at maximum expiration compared with maximum inspiration. The ultrashort TE GRE technique yielded images demonstrating signal from lung parenchyma with minimal motion-induced noise. CONCLUSION: Quantitative in vivo measurements of lung T2* and relative proton density in conjunction with high-signal parenchymal images can be obtained using a set of very rapid breath-hold images with a recently developed ultrashort TE GRE sequence.