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Electronic Nicotine Delivery Systems (ENDS) aerosol exposures can induce endothelial dysfunction (ED) in healthy young humans and animals. Thermal degradation of ENDS solvents, propylene glycol and vegetable glycerin (PG: VG), generates abundant formaldehyde (FA) and other carbonyls. Because FA can activate the transient receptor potential ankyrin-1 (TRPA1) sensor, we hypothesized that FA in ENDS aerosols provokes TRPA1-mediated changes that include ED and 'respiratory braking' - biomarkers of harm. To test this, wild-type (WT) and TRPA1-null mice were exposed by inhalation to either filtered air, PG: VG-derived aerosol, or formaldehyde (FA, 5 ppm). Short-term exposures to PG: VG and FA induced ED in female WT but not in female TRPA1-null mice. Moreover, acute exposures to PG: VG and FA stimulated respiratory braking in WT but not in TRPA1-null female mice. Urinary metabolites of FA (ie, N -1,3-thiazolidine-4-carboxylic acid, TCA; N -1,3-thiazolidine-4-carbonyl glycine, TCG) and monoamines were measured by LC-MS/MS. PG: VG and FA exposures significantly increased urinary excretion of both TCA and TCG in both WT and TRPA1-null mice. To confirm that inhaled FA directly contributed to urinary TCA, mice were exposed to isotopic 13C-FA gas (1 ppm, 6 h).13C-FA exposure significantly increased the urine level of 13C-TCA in the early collection (0-3 h) supporting a direct relationship between inhaled FA and TCA. Collectively, these data suggest that ENDS use may increase CVD risk dependent on FA, TRPA1, and catecholamines, yet independently of either nicotine or flavorants. This study supports that levels of FA in ENDS-derived aerosols should be lowered to mitigate CVD risk in people who use ENDS.
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BACKGROUND: Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy. METHODS: Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). RESULTS: A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. CONCLUSIONS: Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.
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The use of head-mounted augmented reality (AR) for surgeries has grown rapidly in recent years. AR aids in intraoperative surgical navigation through overlaying three-dimensional (3D) holographic reconstructions of medical data. However, performing AR surgeries on complex areas such as the head and neck region poses challenges in terms of accuracy and speed. This study explores the feasibility of an AR guidance system for resections of positive tumour margins in a cadaveric specimen. The authors present an intraoperative solution that enables surgeons to upload and visualize holographic reconstructions of resected cadaver tissues. The solution involves using a 3D scanner to capture detailed scans of the resected tissue, which are subsequently uploaded into our software. The software converts the scans of resected tissues into specimen holograms that are viewable through a head-mounted AR display. By re-aligning these holograms with cadavers with gestures or voice commands, surgeons can navigate the head and neck tumour site. This workflow can run concurrently with frozen section analysis. On average, the authors achieve an uploading time of 2.98 min, visualization time of 1.05 min, and re-alignment time of 4.39 min, compared to the 20 to 30 min typical for frozen section analysis. The authors achieve a mean re-alignment error of 3.1 mm. The authors' software provides a foundation for new research and product development for using AR to navigate complex 3D anatomy in surgery.
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OBJECTIVES: To investigate the association between radiotherapy (RT) and cardiac biomarkers in women with left-sided breast cancer. METHODS: This prospective observational study recruited patients with stage I-III left-sided breast cancer without coronary heart disease who required adjuvant RT. High-sensitivity troponin I(hsTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), and high-sensitivity C-reactive protein(hsCRP) levels were measured pre-RT, immediately after RT, and 3 months post-RT. Cardiac-sparing RT techniques were utilized (Field-in-Field IMRT/VMAT ± voluntary deep inspiration breath-hold). Statistical analyses were performed using non-parametric tests and multivariable quantile regression (QR). RESULTS: One hundred five patients completed the study, with 63 evaluable at three months post-RT. Pre- and post-RT biomarkers showed no significant differences. Median pre-RT and post-RT values were: hsTnI (0.012ng/mL; 0.012ng/mL), hsCRP (3.1 mg/L; 2.8 mg/L), and NT-proBNP (59pg/mL; 45pg/mL). Three months post-RT, hsTnI, hsCRP and NT-proBNP levels also showed no significant differences. Multivariable QR revealed no association between heart Dmean [median(IQR): 2.87 Gy (2.05-3.94)] and post-RT biomarkers. Age and BMI were associated with hsCRP and NT-proBNP, respectively. CONCLUSIONS: hsTnI, NT-proBNP, and hsCRP are not correlated with contemporary low cardiac exposure in left-sided breast cancer patients treated with contemporary RT techniques.
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OBJECTIVES: Social media has enabled discussion of relevant topics within otolaryngology. With increasing academic discourse occurring on virtual platforms, it is important to examine who is influencing these discussions. This study thus aims to: (1) identify the top Twitter influencers in otolaryngology and (2) assess the relationship between Twitter influence and academic impact. STUDY DESIGN: Cross-sectional analysis. SETTING: Twitter. METHODS: The Right Relevance program was used to identify and rank the top 75 Twitter influencers, excluding organizations, according to the search terms "otolaryngology," "head and neck surgery," "ear nose throat," "rhinology," "head and neck," "laryngology," "facial plastics," and "otology." Demographic data and h-index were collected for each influencer. Correlational analyzes were performed to assess the relationships between Twitter rank and geographic location, sex, subspecialty, and h-index. RESULTS: The majority of the top 75 influencers were otolaryngologists (87%), female (68%), and located in the United States (61%). General otolaryngology (n = 20, 31%) was more well-represented than any individual subspecialty including facial plastics (n = 10, 15%), rhinology (n = 10, 15%), and neurotology (n = 9, 14%). There was a significant relationship between Twitter rank and h-index (Spearman ρ value of -0.32; 95% confidence interval: -0.51 to -0.01; P = .006). Twitter rank was not significantly correlated with subspecialty, sex, or geographic location (P > .05). CONCLUSION: The majority of Twitter influencers within otolaryngology were otolaryngologists, female, and located in the United States. Social media influence is positively associated with academic impact among otolaryngologists.
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Otolaringologia , Mídias Sociais , Mídias Sociais/estatística & dados numéricos , Estudos Transversais , Humanos , Feminino , Masculino , Estados UnidosRESUMO
Oligometastatic non-small cell lung cancer (OMD NSCLC) has been proposed to bridge the spectrum between non-metastatic and widely metastatic states and is perceived as an opportunity for potential cure if removed. Twelve clinical trials on local treatment have been reported, yet none are conclusive. These trials informed the development of a joint clinical practice guideline by the American & European Societies for Radiation Oncology, which endorses local treatment for OMD NSCLC. However, the heterogeneity between prognostic factors within these trials likely influenced outcomes and can only support guidance at this time. Caution against an uncritical acceptance of the guideline is discussed, as strong recommendations are offered based on expert opinion and inconclusive evidence. The guideline is also examined by a patient's caregiver, who emphasizes that uncertain evidence impedes shared decision making.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Guias de Prática Clínica como Assunto , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Equipolência Terapêutica , Metástase Neoplásica , Prognóstico , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Aggressive B cell lymphoma with secondary central nervous system (CNS) involvement (SCNSL) carries a dismal prognosis. Chimeric antigen receptor (CAR) T cells (CAR-T) targeting CD19 have revolutionized the treatment for B cell lymphomas; however, only single cases with CNS manifestations successfully treated with CD19 CAR-T have been reported. METHODS: We prospectively enrolled 4 patients with SCNSL into our study to assess clinical responses and monitor T cell immunity. RESULTS: Two of four SNCSL patients responded to the CD19-targeted CAR-T. Only one patient showed a substantial expansion of peripheral (PB) CAR-T cells with an almost 100-fold increase within the first week after CAR-T. The same patient also showed marked neurotoxicity and progression of the SNCSL despite continuous surface expression of CD19 on the lymphoma cells and an accumulation of CD4+ central memory-type CAR-T cells in the CNS. Our studies indicate that the local production of chemokine IP-10, possibly through its receptor CXCR3 expressed on our patient's CAR-T, could potentially have mediated the local accumulation of functionally suboptimal anti-tumor T cells. CONCLUSIONS: Our results demonstrate expansion and homing of CAR-T cells into the CNS in SNCSL patients. Local production of chemokines such as IP-10 may support CNS infiltration by CAR-T cells but also carry the potential of amplifying local toxicity. Future studies investigating numbers, phenotype, and function of CAR-T in the different body compartments of SNSCL patients receiving CAR-T will help to improve local delivery of "fit" and highly tumor-reactive CAR-T with low off-target reactivity into the CNS.
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Neoplasias do Sistema Nervoso Central , Linfoma , Receptores de Antígenos Quiméricos , Humanos , Quimiocina CXCL10 , Neoplasias do Sistema Nervoso Central/terapia , Antígenos CD19RESUMO
OBJECTIVES: Virtual 3D specimen mapping of oncologic surgical specimens provides a visual record of the specimen and margin sampling sites which can be utilized in a variety of cancer care settings. Our objective was to perform a retrospective review of head and neck surgical oncology cases where the specimen was mapped post-operatively and to evaluate the utility of these 3D specimen maps amongst the multidisciplinary cancer care team. METHODS: A retrospective review of our 3D specimen model biorepository was performed. Surgical specimens were 3D scanned and then graphically annotated (or "mapped") during routine pathologic processing. The resulting 3D specimen maps were distributed to the multidisciplinary oncologic care team. Final margin status and any use of the 3D specimen maps were recorded. RESULTS: A total of 28 cases were included. Virtual 3D specimen maps were utilized by the cancer care team in 8 cases (29%), including 2 positive margin cases, 2 close margin cases, and 4 indeterminate margin cases. 3D specimen maps were used to visualize positive margin sites for pathologist-surgeon communication as a visual reference during tumor board discussions and to inform radiation treatment planning. CONCLUSION: Post-operative virtual 3D specimen mapping of oncologic specimens creates a permanent visual record of the specimen and the margins sampled and may serve as a beneficial tool for communication amongst the multidisciplinary cancer care team. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:191-197, 2024.
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Carcinoma de Células Escamosas , Humanos , Estudos Retrospectivos , Carcinoma de Células Escamosas/patologiaRESUMO
BACKGROUND: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. METHODS: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. RESULTS: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. CONCLUSIONS: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.
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Neoplasias de Tecidos Moles , Cirurgia Assistida por Computador , Humanos , Estudos de Viabilidade , Prognóstico , Margens de Excisão , Cirurgia Assistida por Computador/métodos , Estudos RetrospectivosRESUMO
OBJECTIVES: Evaluation of potential gender gaps among Head and Neck (H&N) surgeons can highlight areas for increased support of female H&N surgeons and improve gender diversity within the subspecialty. To evaluate gender trends in representation and career trajectory among recent H&N surgery fellowship graduates. METHODS: This cross-sectional analysis included graduates from Head and Neck Surgery fellowships accredited by the American Head and Neck Society (AHNS) from 2008 to 2018. Additional demographic data was collected via publicly available websites including gender, years in practice, practice location, type of practice, h-index, and academic rank. The primary outcomes were the proportion of female Head and Neck fellowship graduates and gender trends in career trajectory and academic productivity (via h-index). RESULTS: Between 2008 and 2018, 449 surgeons graduated from Head and Neck surgery fellowship with females comprising 99 of 449 graduates (22%). Female representation increased from 1 of 30 (3%) graduates in 2008 to 17 of 52 (33%) in 2018. A proportionally similar number of women graduating fellowship also practiced in an academic setting (23%). There were fewer female assistant, associate and full professors compared with their male counterparts. Women had lower h-indices compared with men even when controlling for years in practice (mean 11.4 vs. 8.2, p < 0.03). CONCLUSION: Despite the increase in women graduating from H&N surgery fellowships, gender disparities within academic rank and academic productivity as measured by h-index remain. While a proportional number of women completing fellowship are entering academic practice, additional investigation and support is needed to address the potential gender gaps identified within academic H&N surgery.
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Otolaringologia , Cirurgiões , Humanos , Masculino , Estados Unidos , Feminino , Bolsas de Estudo , Estudos Transversais , EficiênciaRESUMO
BACKGROUND: Given the complex three-dimensional (3D) anatomy of head and neck cancer specimens, head and neck surgeons often have difficulty relocating the site of an initial positive margin to perform re-resection. This cadaveric study aimed to determine the feasibility and accuracy of augmented reality surgery to guide head and neck cancer re-resections. METHODS: This study investigated three cadaveric specimens. The head and neck resection specimen was 3D scanned and exported to the HoloLens augmented reality environment. The surgeon manually aligned the 3D specimen hologram into the resection bed. Accuracy of manual alignment and time intervals throughout the protocol were recorded. RESULTS: The 20 head and neck cancer resections performed in this study included 13 cutaneous and 7 oral cavity resections. The mean relocation error was 4 mm (range, 1-15 mm) with a standard deviation of 3.9 mm. The mean overall protocol time, from the start of 3D scanning to alignment into the resection bed, was 25.3 ± 8.9 min (range, 13.2-43.2 min). Relocation error did not differ significantly when stratified by greatest dimension of the specimen. The mean relocation error of complex oral cavity composite specimens (maxillectomy and mandibulectomy) differed significantly from that of all the other specimen types (10.7 vs 2.8; p < 0.01). CONCLUSIONS: This cadaveric study demonstrated the feasibility and accuracy of augmented reality to guide re-resection of initial positive margins in head and neck cancer surgery.
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Realidade Aumentada , Neoplasias de Cabeça e Pescoço , Cirurgia Assistida por Computador , Humanos , Estudos de Viabilidade , Neoplasias de Cabeça e Pescoço/cirurgia , Cirurgia Assistida por Computador/métodos , CadáverRESUMO
AbstractTraining of resident physicians is essential for the care of future patients. While surgical trainee involvement is necessary, its disclosure to patients can often be omitted or underplayed by surgeons. The informed consent process and the underlying ethical principles make evident that patients should be informed of trainee involvement. In this review we explore the importance of disclosure, current themes in practice, and the optimal discussion for which we should strive.
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Revelação , Consentimento Livre e Esclarecido , HumanosRESUMO
The advent of computed tomography-based planning coupled with modern tools for target delineation and hypofractionated treatment schedules has increased efficiency and throughput for patients with breast cancer. While the benefit of adjuvant radiation therapy (RT) in reducing locoregional recurrences is established, disentangling local versus regional recurrence risks with modern treatment protocols has become an area of active research to de-escalate treatment. Delineation guidelines for nodal regions either attempt to replicate results of conventional RT techniques by translating bony landmarks to clinical target volumes or use landmarks based on the fact that lymphatic channels run along the vasculature. Because direct comparisons of both approaches are implausible, mapping studies of nodal recurrences have reported on the proportion of nodes included in these delineation guidelines, and larger, bony, landmark-based guidelines appear intuitively appealing for patients with unfavorable risk factors. A pooled analysis of these studies is reported here, along with literature supporting the exclusion of the true chest wall from postmastectomy/breast-conserving surgery clinical target volumes and the selective (versus routine) use of bolus during postmastectomy RT. The risk-adapted approach suggested here accounts for the risk of recurrence as well as toxicity and endorses nuanced target volume delineation rather than a one-size-fits-all approach.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/radioterapia , Mastectomia , Recidiva Local de Neoplasia/cirurgia , Mastectomia Segmentar , Tomografia Computadorizada por Raios XRESUMO
Structured light three-dimensional (3D) scanning is a ubiquitous mainstay of object inspection and quality control in industrial manufacturing, and has recently been integrated into various medical disciplines. Photorealistic 3D scans can readily be acquired from fresh or formalin-fixed tissue and have potential for use within anatomic pathology (AP) in a variety of scenarios, ranging from direct clinical care to documentation and education. Methods for scanning and post-processing of fresh surgical specimens rely on relatively low-cost and technically simple procedures. Here, we demonstrate potential use of 3D scanning in surgical pathology in the form of a mixed media pathology report with a novel post-scan virtual inking and marking technique to precisely demarcate areas of tissue sectioning and details of final tumor and margin status. We display a sample mixed-media pathology report (3D specimen map) which integrates 3D and conventional pathology reporting methods. Finally, we describe the potential utility of 3D specimen modeling in both didactic and experiential teaching of gross pathology lab procedures.
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We have implemented a novel intraoperative communication system for head and neck surgical pathology using 3D scanning technology and computer-aided design (CAD) software. Here, we highlight our CAD margin protocol, in which we 3D scan head and neck oncologic surgical specimens and map frozen section results. This enhances the communication of margin status between surgeons and pathologists and delivers visual anatomic guidance for re-resection when needed. Laryngoscope, 133:1914-1918, 2023.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas/patologia , Secções Congeladas , Desenho Assistido por Computador , Margens de ExcisãoRESUMO
OBJECTIVE: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). METHODS: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. RESULTS: The median OS was 71.4 months (interquartile range: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89-0.98); 0.94 (0.89-0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09-0.53); 0.30 (0.12-0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01-1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08-6.57)] and adventitial involvement [2.54 (1.36-4.72)] also influenced OS, while involved margins [3.12 (1.24-7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44-0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57-0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. CONCLUSION: NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. ADVANCES IN KNOWLEDGE: The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Resultado do Tratamento , Terapia Combinada , Carcinoma de Células Escamosas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Prognóstico , Estudos Retrospectivos , Estadiamento de NeoplasiasRESUMO
After oncologic resection of malignant tumors, specimens are sent to pathology for processing to determine the surgical margin status. These results are communicated in the form of a written pathology report. The current standard-of-care pathology report provides a written description of the specimen and the sites of margin sampling without any visual representation of the resected tissue. The specimen itself is typically destroyed during sectioning and analysis. This often leads to challenging communication between pathologists and surgeons when the final pathology report is confirmed. Furthermore, surgeons and pathologists are the only members of the multidisciplinary cancer care team to visualize the resected cancer specimen. We have developed a 3D scanning and specimen mapping protocol to address this unmet need. Computer-aided design (CAD) software is used to annotate the virtual specimen clearly showing sites of inking and margin sampling. This map can be utilized by various members of the multidisciplinary cancer care team.
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Neoplasias , Humanos , Neoplasias/cirurgia , Manejo de Espécimes/métodosRESUMO
OBJECTIVE: To assess in-vivo cross-sectional and 3D morphology of human motor units in hand, forearm and lower leg muscles using magnetic resonance imaging (MRI). METHODS: Diffusion weighted MRI was used with in-scanner electrical stimulation in healthy controls to image motor units at a single slice in lower leg, forearm and hand muscles (n = 6) and multiple slices in the lower leg for 3D assessment (n = 7). RESULTS: Motor unit cross-sectional area (CSA) and maximum Feret diameter (FDmax) did not differ between the lower leg (CSA: 22.4 ± 8.4 mm2; FDmax: 8.7 ± 2.4 mm), forearm (CSA: 23.6 ± 14.1 mm2; FDmax: 9.0 ± 3.3 mm) and hand (CSA: 26.8 ± 12.8 mm2 and FDmax: 9.6 ± 2.7 mm) (ANOVA; p = 0.487 and p = 0.587, respectively). Lower leg motor units were 8.0 ± 3.8 cm long with largest CSA in the motor unit's middle section. 3D motor unit imaging revealed a complex structure with several units splitting and re-forming along their length. CONCLUSIONS: Motor unit MRI (MUMRI) can be applied to upper limb muscles, and can reveal the 3D structure of human motor units in-vivo. SIGNIFICANCE: MUMRI provides the first in-vivo 2D images of upper limb motor units and 3D images of lower leg motor units. 3D imaging suggest a more complex human motor unit structure than previously thought.