Deep Brain Stimulation for Primary Refractory Tinnitus: A Systematic Review.

BACKGROUND: tinnitus is a common and often debilitating condition with limited evidence-based treatment options. Deep brain stimulation (DBS) is an approved treatment modality for certain neurological conditions; its experimental use as a treatment modality for severe tinnitus is novel and beginning to show promise. This systematic review focuses on the current evidence for the safety and efficacy of DBS for treatment of refractory tinnitus. METHODS: a systematic search in PubMed and EMBASE was performed to identify peer-reviewed studies on DBS of non-cortical structures for the primary indication of tinnitus treatment. Three studies were identified as meeting these criteria, one of which had two related sub-studies. RESULTS: seven patients with available data who underwent DBS for tinnitus were identified. DBS targets included nucleus accumbens (NAc), ventral anterior limb of the internal capsule (vALIC), caudate nucleus, and the medial geniculate body (MGB) of the thalamus. All studies used the Tinnitus Functional Index (TFI) as a primary outcome measure. DBS of the caudate was most commonly reported (n = 5), with a mean TFI improvement of 23.3 points. Only one subject underwent DBS targeting the NAc/vALIC (extrapolated TFI improvement 46.8) and one subject underwent DBS targeting the MGB (TFI improvement 59 points). CONCLUSIONS: DBS is a promising treatment option for refractory subjective tinnitus, with early data, from small patient cohorts in multiple studies, suggesting its safety and efficacy. Further studies with a larger patient population are needed to support this safety and efficacy before implementing this treatment to daily practice.

Automatic hepatic tumor segmentation in intra-operative ultrasound: a supervised deep-learning approach.

Purpose: Training and evaluation of the performance of a supervised deep-learning model for the segmentation of hepatic tumors from intraoperative US (iUS) images, with the purpose of improving the accuracy of tumor margin assessment during liver surgeries and the detection of lesions during colorectal surgeries. Approach: In this retrospective study, a U-Net network was trained with the nnU-Net framework in different configurations for the segmentation of CRLM from iUS. The model was trained on B-mode intraoperative hepatic US images, hand-labeled by an expert clinician. The model was tested on an independent set of similar images. The average age of the study population was 61.9 ± 9.9 years. Ground truth for the test set was provided by a radiologist, and three extra delineation sets were used for the computation of inter-observer variability. Results: The presented model achieved a DSC of 0.84 (p=0.0037), which is comparable to the expert human raters scores. The model segmented hypoechoic and mixed lesions more accurately (DSC of 0.89 and 0.88, respectively) than hyper- and isoechoic ones (DSC of 0.70 and 0.60, respectively) only missing isoechoic or >20 mm in diameter (8% of the tumors) lesions. The inclusion of extra margins of probable tumor tissue around the lesions in the training ground truth resulted in lower DSCs of 0.75 (p=0.0022). Conclusion: The model can accurately segment hepatic tumors from iUS images and has the potential to speed up the resection margin definition during surgeries and the detection of lesion in screenings by automating iUS assessment.

Survival difference between patients with single versus multiple metastatic lymph nodes and the role of histology in pathological stage II-N1 non-small cell lung cancer.

BACKGROUND: Previous studies investigating whether metastatic lymph node count is a relevant prognostic factor in pathological N1 non-small cell lung cancer (NSCLC), showed conflicting results. Hypothesizing that outcome may also be related to histological features, we determined the prognostic impact of single versus multiple metastatic lymph nodes in different histological subtypes for patients with stage II-N1 NSCLC. METHODS: We performed a retrospective cohort study using data from the Netherlands Cancer Registry, including patients treated with a surgical resection for stage II-N1 NSCLC (TNM 7th edition) in 2010-2016. Overall survival (OS) was assessed for patients with single (pN1a) and multiple (pN1b) metastatic nodes. Using multivariable analysis, we compared OS between pN1a and pN1b in different histological subtypes. RESULTS: After complete resection of histologically proven stage II-N1 NSCLC, 1309 patients were analyzed, comprising 871 patients with pN1a and 438 with pN1b. The median number of pathologically examined nodes (N1 + N2) was 9 (interquartile range 6-13). Five-year OS was 53% for pN1a versus 51% for pN1b. In multivariable analysis, OS was significantly different between pN1a and pN1b (HR 1.19, 95% CI 1.01-1.40). When stratifying for histology, the prognostic impact of pN1a/b was only observed in adenocarcinoma patients (HR 1.44, 95% CI 1.15-1.81). CONCLUSION: Among patients with stage II-N1 adenocarcinoma, the presence of multiple metastatic nodes had a significant impact on survival, which was not observed for other histological subtypes. If further refinement as to lymph node count will be considered for incorporation into a new staging system, evaluation of the role of histology is recommended.

Correlation between Serum Biomarkers and Lung Ultrasound in COVID-19: An Observational Study.

Serum biomarkers and lung ultrasound are important measures for prognostication and treatment allocation in patients with COVID-19. Currently, there is a paucity of studies investigating relationships between serum biomarkers and ultrasonographic biomarkers derived from lung ultrasound. This study aims to assess correlations between serum biomarkers and lung ultrasound findings. This study is a secondary analysis of four prospective observational studies in adult patients with COVID-19. Serum biomarkers included markers of epithelial injury, endothelial dysfunction and immune activation. The primary outcome was the correlation between biomarker concentrations and lung ultrasound score assessed with Pearson's (r) or Spearman's (rs) correlations. Forty-four patients (67 [41-88] years old, 25% female, 52% ICU patients) were included. GAS6 (rs = 0.39), CRP (rs = 0.42) and SP-D (rs = 0.36) were correlated with lung ultrasound scores. ANG-1 (rs = -0.39) was inversely correlated with lung ultrasound scores. No correlations were found between lung ultrasound score and several other serum biomarkers. In patients with COVID-19, several serum biomarkers of epithelial injury, endothelial dysfunction and immune activation correlated with lung ultrasound findings. The lack of correlations with certain biomarkers could offer opportunities for precise prognostication and targeted therapeutic interventions by integrating these unlinked biomarkers.

Ultrasound guidance in navigated liver surgery: toward deep-learning enhanced compensation of deformation and organ motion.

PURPOSE: Accuracy of image-guided liver surgery is challenged by deformation of the liver during the procedure. This study aims at improving navigation accuracy by using intraoperative deep learning segmentation and nonrigid registration of hepatic vasculature from ultrasound (US) images to compensate for changes in liver position and deformation. METHODS: This was a single-center prospective study of patients with liver metastases from any origin. Electromagnetic tracking was used to follow US and liver movement. A preoperative 3D model of the liver, including liver lesions, and hepatic and portal vasculature, was registered with the intraoperative organ position. Hepatic vasculature was segmented using a reduced 3D U-Net and registered to preoperative imaging after initial alignment followed by nonrigid registration. Accuracy was assessed as Euclidean distance between the tumor center imaged in the intraoperative US and the registered preoperative image. RESULTS: Median target registration error (TRE) after initial alignment was 11.6 mm in 25 procedures and improved to 6.9 mm after nonrigid registration (p = 0.0076). The number of TREs above 10 mm halved from 16 to 8 after nonrigid registration. In 9 cases, registration was performed twice after failure of the first attempt. The first registration cycle was completed in median 11 min (8:00-18:45 min) and a second in 5 min (2:30-10:20 min). CONCLUSION: This novel registration workflow using automatic vascular detection and nonrigid registration allows to accurately localize liver lesions. Further automation in the workflow is required in initial alignment and classification accuracy.

[Current diagnostics and treatment options for tinnitus]. / Diagnostiek en behandelopties voor tinnitus.

Tinnitus is a common condition with great variability in the intensity of symptomatology. In recent years, more and more insights have been gained into the mechanism of tinnitus and its relationship with hearing loss and other factors such as stress. Depending on the symptoms and clinical findings, a patient may be referred to an ENT specialist or audiologist. For the majority of patients, re-assurance and providing good information is sufficient. For others improving hearing and possibly cognitive behavioral therapy remains the most important pillars for treatment of tinnitus. A number of experimental treatments are currently underway which offer hope for the future.

Early response evaluation of PD-1 blockade in NSCLC patients through FDG-PET-CT and T cell profiling of tumor-draining lymph nodes.

Better biomarkers for programmed death - (ligand) 1 (PD-(L)1) checkpoint blockade in non-small cell lung cancer (NSCLC) are needed. We explored the predictive value of early response evaluation using Fluor-18-deoxyglucose positron emission tomography and pre- and on-treatment flowcytometric T-cell profiling in peripheral blood and tumor-draining lymph nodes (TDLN). The on-treatment evaluation was performed 7-14 days after the start of PD-1 blockade in NSCLC patients. These data were related to (pathological) tumor response, progression-free survival, and overall survival (OS). We found that increases in total lesion glycolysis (TLG) had a strong reverse correlation with OS (r = -0.93, p = 0.022). Additionally, responders showed decreased progressors and increased Treg frequencies on-treatment. Frequencies of detectable PD-1-expressing CD8+ T cells decreased in responders but remained stable in progressors. This was especially found in the TDLN. Changes in activated Treg rates in TDLN were strongly but, due to low numbers of data points, non-significantly correlated with ΔTLG and reversely correlated with OS.

Monitoring of pulmonary involvement in critically ill COVID-19 patients - should lung ultrasound be preferred over CT?

BACKGROUND: It is unclear if relevant changes in pulmonary involvement in critically ill COVID-19 patients can be reliably detected by the CT severity score (CTSS) and lung ultrasound score (LUSS), or if these changes have prognostic implications. In addition, it has been argued that adding pleural abnormalities to the LUSS could improve its prognostic value. The objective of this study was to compare LUSS and CTSS for the monitoring of COVID-19 pulmonary involvement through: first, establishing the correlation of LUSS (± pleural abnormalities) and CTSS throughout admission; second, assessing agreement and measurement error between raters for LUSS, pleural abnormalities, and CTSS; third, evaluating the association of the LUSS (± pleural abnormalities) and CTSS with mortality at different timepoints. METHODS: This is a prospective, observational study, conducted during the second COVID-19 wave at the AmsterdamUMC, location VUmc. Adult COVID-19 ICU patients were prospectively included when a CT or a 12-zone LUS was performed at admission or at weekly intervals according to local protocol. Patients were followed 90 days or until death. We calculated the: (1) Correlation of the LUSS (± pleural abnormalities) and CTSS throughout admission with mixed models; (2) Intra-class correlation coefficients (ICCs) and smallest detectable changes (SDCs) between raters; (3) Association between the LUSS (± pleural abnormalities) and CTSS with mixed models. RESULTS: 82 consecutive patients were included. Correlation between LUSS and CTSS was 0.45 (95% CI 0.31-0.59). ICCs for LUSS, pleural abnormalities, and CTSS were 0.88 (95% CI 0.73-0.95), 0.94 (95% CI 0.90-0.96), and 0.84 (95% CI 0.65-0.93), with SDCs of 4.8, 1.4, and 3.9. The LUSS was associated with mortality in week 2, with a score difference between patients who survived or died greater than its SDC. Addition of pleural abnormalities was not beneficial. The CTSS was associated with mortality only in week 1, but with a score difference less than its SDC. CONCLUSIONS: LUSS correlated with CTSS throughout ICU admission but performed similar or better at agreement between raters and mortality prognostication. Given the benefits of LUS over CT, it should be preferred as initial monitoring tool.

Concise Versus Extended Lung Ultrasound Score to Monitor Critically Ill Patients With COVID-19.

BACKGROUND: Lung ultrasound (LUS) can be used to monitor critically ill patients with COVID-19, but the optimal number of examined lung zones is disputed. METHODS: This was a prospective observational study. The objective was to investigate whether concise (6 zones) and extended (12 zones) LUS scoring protocols are clinically equivalent in critically ill ICU subjects with COVID-19. The primary outcome of this study was (statistical) agreement between concise and extended LUS score index evaluated in both supine and prone position. Agreement was determined using correlation coefficients and Bland-Altman plots to detect systematic differences between protocols. Secondary outcomes were difference between LUS score index in supine and prone position using similar methods. RESULTS: We included 130 LUS examinations in 40 subjects (mean age 69.0 ± 8.5y, 75% male). Agreement between concise and extended LUS score index had no clinically relevant constant or proportional bias and limits of agreement were below the smallest detectable change. Across position changes, supine LUS score index was 8% higher than prone LUS score index and had limits above the smallest detectable change, indicating true LUS score index differences between protocols may occur due to the position change itself. Lastly, inter-rater and intra-rater agreement were very good. CONCLUSIONS: Concise LUS was equally informative as extended LUS for monitoring critically ill subjects with COVID-19 in supine or prone position. Clinicians can monitor patients undergoing position changes but must be wary that LUS score index alterations may result from the position change itself rather than disease progression or clinical improvement.

The Impact of Thoracic Ultrasound on Clinical Management of Critically Ill Patients (UltraMan): An International Prospective Observational Study.

OBJECTIVES: To investigate the impact of thoracic ultrasound (TUS) examinations on clinical management in adult ICU patients. DESIGN: A prospective international observational study. SETTING: Four centers in The Netherlands and Italy. PATIENTS: Adult ICU patients (> 18 yr) that received a clinically indicated lung ultrasound examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinicians performing TUS completed a pre- and post-examination case report form. Patient characteristics, TUS, and resulting clinical effects were recorded. First, change of management, defined as a TUS-induced change in clinical impression leading to a change in treatment plan, was reported. Second, execution of intended management changes within 8 hours was verified. Third, change in fluid balance after 8 hours was calculated. A total of 725 TUS performed by 111 operators across 534 patients (mean age 63 ± 15.0, 70% male) were included. Almost half of TUS caused a change in clinical impression, which resulted in change of management in 39% of cases. The remainder of TUS confirmed the clinical impression, while a minority (4%) did not contribute. Eighty-nine percent of management changes indicated by TUS were executed within 8 hours. TUS examinations that led to a change in fluid management also led to distinct and appropriate changes in patient's fluid balance. CONCLUSIONS: In this international observational study in adult ICU patients, use of TUS had a major impact on clinical management. These results provide grounds for future randomized controlled trials to determine if TUS-induced changes in decision-making also lead to improved health outcomes.

Radiofrequency Ablation for Inferior Turbinate Hypertrophy: Predictive Factors for Short and Long-Term Outcomes.

OBJECTIVES: Radiofrequency Ablation (RFA) is a widely used technique for treatment of nasal obstruction due to inferior turbinate hypertrophy. This study aims to evaluate short and long-term outcome after RFA. Secondly, predictive factors for this outcome were evaluated. METHODS: A prospective clinical study was performed in 65 patients to evaluate short-term outcome and predictive factors (Study A). To evaluate long-term outcome and predictive factors we performed a second clinical study in 124 patients (Study B). Patients scored nasal symptoms on a 1 to 5 points visual analogue scale (VAS) and filled in questionnaires about their comorbidity, previous nasal surgery, and medication use. RESULTS: Study A: There was significant short-term (6-8 weeks after RFA) improvement in nasal obstruction (VAS -1.3, P < .001), trouble exercising (VAS -1.5, P < .001), trouble sleeping (VAS -0.9, P < .001), snoring (VAS -1.1, P< .001), and hyposmia (VAS -0.6, P = .004). Smoking (R2 = .065, P = .047) was a predictor for less optimized and previous use of decongestive nasal spray (R2 = .135, P = .005) for better short-term outcome. Study B: Nasal obstruction significantly decreased in the long term (1-5 years after RFA) compared to VAS before RFA (VAS -1.5, P < .001), but slightly increased compared to VAS 6 to 8 weeks after RFA (VAS +0.3, P = .036). Allergy (R2 = .066, P = .006), asthma (R2 = .068, P = .005), and previous use of corticosteroid nasal spray (R2 = .050, P = .016) were associated with a less optimized and older age (R2 = .217, P < .001) with better long-term outcome. CONCLUSION: RFA is an efficient treatment for nasal obstruction, and improves sleeping, exercising, snoring, and hyposmia. Predictors for good short-term outcome were previous use of decongestive nasal spray and no smoking. Predictors for a less optimized long-term outcome were allergy, asthma, and previous use of corticosteroid nasal spray. Older age was associated with better long-term outcome.

INCIDENCE, RISK FACTORS, AND OUTCOME OF SUSPECTED CENTRAL VENOUS CATHETER-RELATED INFECTIONS IN CRITICALLY ILL COVID-19 PATIENTS: A MULTICENTER RETROSPECTIVE COHORT STUDY.

ABSTRACT: Background: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with mortality in critically ill COVID-19 patients. Methods: This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic health record database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. Results: In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1,000 catheter indwelling days, respectively. Prone ventilation for more than 5 days was associated with increased risk of suspected catheter-related infection; odds ratio, 5.05 (95% confidence interval 2.12-11.0). Risk of death was significantly higher in patients with suspected catheter-related infection (hazard ratio, 1.78; 95% confidence interval, 1.25-2.53). Conclusions: This study shows that in critically ill patients with COVID-19, prevalence and incidence of suspected catheter-related infection are high, prone ventilation is a risk factor, and mortality is higher in case of catheter-related infection.

Post-Mortem Analysis of Neuropathological Changes in Human Tinnitus.

Tinnitus is the phantom perception of a sound, often accompanied by increased anxiety and depressive symptoms. Degenerative or inflammatory processes, as well as changes in monoaminergic systems, have been suggested as potential underlying mechanisms. Herein, we conducted the first post-mortem histopathological assessment to reveal detailed structural changes in tinnitus patients' auditory and non-auditory brain regions. Tissue blocks containing the medial geniculate body (MGB), thalamic reticular nucleus (TRN), central part of the inferior colliculus (CIC), and dorsal and obscurus raphe nuclei (DRN and ROb) were obtained from tinnitus patients and matched controls. Cell density and size were assessed in Nissl-stained sections. Astrocytes and microglia were assessed using immunohistochemistry. The DRN was stained using antibodies raised against phenylalanine hydroxylase-8 (PH8) and tyrosine-hydroxylase (TH) to visualize serotonergic and dopaminergic cells, respectively. Cell density in the MGB and CIC of tinnitus patients was reduced, accompanied by a reduction in the number of astrocytes in the CIC only. Quantification of cell surface size did not reveal any significant difference in any of the investigated brain regions between groups. The number of PH8-positive cells was reduced in the DRN and ROb of tinnitus patients compared to controls, while the number of TH-positive cells remained unchanged in the DRN. These findings suggest that both neurodegenerative and inflammatory processes in the MGB and CIC underlie the neuropathology of tinnitus. Moreover, the reduced number of serotonergic cell bodies in tinnitus cases points toward a potential role of the raphe serotonergic system in tinnitus.

The Effect of Noise Trauma and Deep Brain Stimulation of the Medial Geniculate Body on Tissue Activity in the Auditory Pathway.

Tinnitus is defined as the phantom perception of sound. To date, there is no curative treatment, and contemporary treatments have failed to show beneficial outcomes. Deep brain stimulation has been suggested as a potential therapy for refractory tinnitus. However, the optimal target and stimulation regimens remain to be defined. Herein, we investigated metabolic and neuronal activity changes using cytochrome C oxidase histochemistry and c-Fos immunohistochemistry in a noise trauma-induced rat model of tinnitus. We also assessed changes in neuronal activity following medial geniculate body (MGB) high-frequency stimulation (HFS). Metabolic activity was reduced in the primary auditory cortex, MGB and CA1 region of the hippocampus in noise-exposed rats. Additionally, c-Fos expression was increased in the primary auditory cortex of those animals. Furthermore, MGB-HFS enhanced c-Fos expression in the thalamic reticular nucleus. We concluded that noise trauma alters tissue activity in multiple brain areas including the auditory and limbic regions. MGB-HFS resulted in higher neuronal activity in the thalamic reticular nucleus. Given the prominent role of the auditory thalamus in tinnitus, these data provide more rationales towards targeting the MGB with HFS as a symptom management tool in tinnitus.

Evolution of Respiratory Muscles Thickness in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Given the long ventilation times of patients with COVID-19 that can cause atrophy and contractile weakness of respiratory muscle fibers, assessment of changes at the bedside would be interesting. As such, the aim of this study was to determine the evolution of respiratory muscle thickness assessed by ultrasound. METHODS: Adult (> 18 y old) patients admitted to the ICU who tested positive for SARS-CoV-2 and were ventilated for < 24 h were consecutively included. The first ultrasound examination (diaphragm, rectus abdominis, and lateral abdominal wall muscles) was performed within 24 h of intubation and regarded as baseline measurement. After that, each following day an additional examination was performed, for a maximum of 8 examinations per subject. RESULTS: In total, 30 subjects were included, of which 11 showed ≥ 10% decrease in diaphragm thickness from baseline; 10 showed < 10% change, and 9 showed ≥ 10% increase from baseline. Symptom duration before intubation was highest in the decrease group (12 [11-14] d, P = .03). Total time ventilated within the first week was lowest in the increase group (156 [129-172] h, P = .03). Average initial diaphragm thickness was 1.4 (1.1-1.6) mm and did not differ from final average thickness (1.3 [1.1-1.5] mm, P = .54). The rectus abdominis did not show statistically significant changes, whereas lateral abdominal wall thickness decreased from 14 [10-16] mm at baseline to 11 [9-13] mm on the last day of mechanical ventilation (P = .08). Mixed-effect linear regression demonstrated an association of atrophy and neuromuscular-blocking agent (NMBA) use (P = .01). CONCLUSIONS: In ventilated subjects with COVID-19, overall no change in diaphragm thickness was observed. Subjects with decreased or unchanged thickness had a longer ventilation time than those with increased thickness. NMBA use was associated with decreased thickness. Rectus muscle thickness did not change over time, whereas lateral abdominal muscle thickness decreased but this change was not statistically significant.

Lung Ultrasound Signs to Diagnose and Discriminate Interstitial Syndromes in ICU Patients: A Diagnostic Accuracy Study in Two Cohorts.

OBJECTIVES: To determine the diagnostic accuracy of lung ultrasound signs for both the diagnosis of interstitial syndrome and for the discrimination of noncardiogenic interstitial syndrome (NCIS) from cardiogenic pulmonary edema (CPE) in a mixed ICU population. DESIGN: A prospective diagnostic accuracy study with derivation and validation cohorts. SETTING: Three academic mixed ICUs in the Netherlands. PATIENTS: Consecutive adult ICU patients that received a lung ultrasound examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULT: The reference standard was the diagnosis of interstitial syndrome (NCIS or CPE) or noninterstitial syndromes (other pulmonary diagnoses and no pulmonary diagnoses) based on full post-hoc clinical chart review except lung ultrasound. The index test was a lung ultrasound examination performed and scored by a researcher blinded to clinical information. A total of 101 patients were included in the derivation and 122 in validation cohort. In the derivation cohort, patients with interstitial syndrome ( n = 56) were reliably discriminated from other patients based on the presence of a B-pattern (defined as greater than or equal to 3 B-lines in one frame) with an accuracy of 94.7% (sensitivity, 90.9%; specificity, 91.1%). For discrimination of NCIS ( n = 29) from CPE ( n = 27), the presence of bilateral pleural line abnormalities (at least two: fragmented, thickened or irregular) had the highest diagnostic accuracy (94.6%; sensitivity, 89.3%; specificity, 100%). A diagnostic algorithm (Bedside Lung Ultrasound for Interstitial Syndrome Hierarchy protocol) using B-pattern and bilateral pleural abnormalities had an accuracy of 0.86 (95% CI, 0.77-0.95) for diagnosis and discrimination of interstitial syndromes. In the validation cohort, which included 122 patients with interstitial syndrome, bilateral pleural line abnormalities discriminated NCIS ( n = 98) from CPE ( n = 24) with a sensitivity of 31% (95% CI, 21-40%) and a specificity of 100% (95% CI, 86-100%). CONCLUSIONS: Lung ultrasound can diagnose and discriminate interstitial syndromes in ICU patients with moderate-to-good accuracy. Pleural line abnormalities are highly specific for NCIS, but sensitivity is limited.

Anatomical Variation in Diaphragm Thickness Assessed with Ultrasound in Healthy Volunteers.

Ultrasonography of the diaphragm in the zone of apposition has become increasingly popular to evaluate muscle thickness and thickening fraction. However, measurements in this anatomical location are frequently hindered by factors that constrain physical accessibility or that alter diaphragm position. Therefore, other anatomical positions at the chest wall for transducer placement are used, but the variability in diaphragm thickness across the dome has not been systematically studied. The aim of this study was to evaluate anatomical variation of diaphragm thickness in 46 healthy volunteers on three ventrodorsal lines and two craniocaudal positions on these three lines. The intraclass correlation coefficient (ICC) for diaphragm thickness in the craniocaudal direction on the mid-axillary line was significantly higher than those on the posterior axillary and midclavicular lines, suggesting it had the lowest variability (ICCmidaxillary = .89, 95% confidence interval [CI]: 0.83-0.93, ICCposterior axillary = 0.74, 95% CI: 0.62-0.85, ICCmidclavicular = 0.62, 95% CI: 0.43-0.47, p < 0.05). Average diaphragm thickness was comparable on the posterior axillary and midaxillary lines and substantially larger on the midclavicular line (1.24 mm [1.06-1.47], 1.27 mm [1.10-1.42] and 2.32 [1.97-2.70], p < 0.01). We conclude that the normal diaphragm has a large variability in thickness, especially in the ventrodorsal direction. Variability in craniocaudal position is the lowest at the midaxillary line, which therefore appears to be the preferred site for diaphragm thickness measurement.