The clinical spectrum of MELAS and associated disorders across ages: a retrospective cohort study.

Objective: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disease, although some have a milder phenotype. We aimed to evaluate the clinical spectrum of this disease from MELAS patients to asymptomatic carriers and identify predictors of severity. Methods: We reviewed 81 patients, who had MELAS or had positive genetics without meeting clinical criteria. Patients who met criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE) were categorized as MELAS, symptomatic non-MELAS, and asymptomatic. MELAS was further categorized as "standard-onset" if the first stroke-like episode (SLE) occurred before age 40 or "late-onset." Results: Eighty-one patients were included: 42 MELAS (13 late-onset), 30 symptomatic non-MELAS, and 9 asymptomatic. MELAS patients had lower BMI at onset (mean 18.6 vs. 25.1 asymptomatic and 22.0 symptomatic non-MELAS, p < 0.05). There was a trend toward higher serum heteroplasmy in MELAS compared to symptomatic non-MELAS and asymptomatic (means 39.3, 29.3, and 21.8% p = 0.09). Symptomatic non-MELAS had more sensorineural hearing loss as first presenting symptom (51.6% vs. 24.4%, p < 0.05). MELAS had higher prevalence of seizures (88.1% vs. 16.7%, p < 0.05) and shorter survival from onset to death (50% mortality at 25 years vs. 10%, p < 0.05). Late-onset MELAS had longer disease duration from first symptom to first SLE (mean 16.6 vs. 9.3 yrs) and also lived longer (mean age at death 62 vs. 30). Standard-onset MELAS had more neurologic involvement at onset than late-onset (51.7% vs. 15.4%). Late-onset patients had more prevalent diabetes (69.2% vs. 13.8%) and nephropathy (53.8% vs. 10.3%). Patients with late-onset MELAS also had more organ systems involved (mean 4.1 vs. 2.7, p < 0.05). There was a trend toward higher heteroplasmy levels in standard-onset (mean 44.8% vs. 25.3%, p = 0.18). Discussion: Our study highlights the spectrum of MELAS. The lower BMI in MELAS at presentation as well as higher rates of sensorineural hearing loss as initial symptom in symptomatic non-MELAS may be useful clinical markers. While many patients present before age 40 with SLE, some can present with SLE later in life. Standard onset MELAS is more likely to present with neurologic symptoms. Late-onset is more likely to suffer diabetes or nephropathy and have more organ systems involved.

Implications of intracranial hemorrhage associated with stereo-EEG.

OBJECTIVE: Intracranial hemorrhage (ICH) is a known complication during stereo-electroencephalography (sEEG) however true rates remain unknown. We provide a comprehensive review of ICH during sEEG regardless of clinical symptoms. Secondly, we analyzed sEEG recordings to identify electrographic correlates of ICH. METHODS: This is a retrospective study of patients undergoing sEEG between January 2016 and April 2022 at the Mayo Clinic in Rochester. We reviewed medical records and imaging studies to identify ICH. We analyzed ICH by type, electrode trajectories, timing, sEEG findings and outcomes. RESULTS: There were a total of 201 sEEG implants, of which 23 (11%) cases or 0.9% electrodes implanted had evidence of ICH. The majority of affected patients (82%) were either asymptomatic or had mild clinical neurological manifestations. In 90% of patients who proceeded with surgical treatments, outcomes were favorable. The most common sEEG finding in contacts in proximity of ICH was either focal slowing with interictal discharges or focal electrographic seizures. CONCLUSIONS: ICH associated with sEEG is likely under-reported in literature. We present electroencephalographic correlates of ICH that may aid identification of ICH in the course of performing sEEG monitoring. SIGNIFICANCE: Our data provides clinically relevant information on potential risks and outcomes of ICH. Furthermore, our findings aid identification of ICH during sEEG.

EEG Source Localization in Temporal Encephaloceles: Concordance With Surgical Resection and Clinical Outcomes.

PURPOSE: Temporal encephaloceles are a cause of drug-resistant temporal lobe epilepsy; however, their relationship with epileptogenesis is unclear, and optimal surgical resection is uncertain. EEG source localization (ESL) may guide surgical decision-making. METHODS: We reviewed patients at Mayo Clinic Rochester with drug-resistant temporal lobe epilepsy and temporal encephaloceles, who underwent limited resection and had 1-year outcomes. EEG source localization was performed using standard density scalp EEG of ictal and interictal activity. Distance from dipole and standardized low-resolution brain electromagnetic tomography (sLORETA) solutions to the encephalocele were measured. Concordance of ESL with encephalocele and surgical resection was compared with 1-year surgical outcomes. RESULTS: Seventeen patients met criteria. The mean distances from ESL results to encephalocele center for dipole and sLORETA analyses were 23 mm (SD 9) and 22 mm (SD 11), respectively. Ten patients (55.6%) had Engel I outcomes at 1 year. Dipole-encephalocele distance and sLORETA-encephalocele distance were significantly longer in patients with Engel I outcome and patients whose encephalocele was contained by sLORETA had worse outcome as well; however, multiple logistic regression analysis found that only containment of encephalocele by the sLORETA current density was significant (P < 0.05), odds ratio 0.12 (95% confidence interval [0.021, 0.71]). CONCLUSIONS: EEG source localization of scalp EEG localizes near encephaloceles, however, typically not in the encephalocele itself; this may be due to scalp EEG sampling propagated activity or alternatively that the seizure onset zone extends beyond the herniated cortex. Surprisingly, we observed increased ESL to encephalocele distances in patients with excellent surgical outcomes. Larger cohort studies including intracranial EEG data are needed to further explore this finding.

Understanding lower limb blood flow occlusion parameters for use in field-based settings.

Reduction of blood flow to the limb using cuffs before or during exercise has become increasingly popular for training and rehabilitation. Our study tested the effects of cuff brand/width on pressures required to reach limb occlusion pressure (LOP) and developed, cross-validated, and compared accuracy of two LOP prediction equations to previously created methods. Supine LOP was determined in the distal popliteal artery using four different cuff brands/widths in 23 adult participants. Participants then had demographic and resting variables assessed, and two LOP prediction equations were developed from these variables and were compared to five previously developed models and a method using posterior tibial artery palpation for LOP assessment in an independent sample (n = 14 adult runners). For cuff comparison, the widest two cuffs had significantly lower LOP (mean ~149 mmHg) than the narrowest cuffs (mean ~176 mmHg), with the narrowest cuff unable to reach LOP. The eight methods used to predict LOP ranged in accuracy (mean absolute percent errors 3.9-23.0%), with highest accuracy in equations using mean arterial pressure (MAP) and BMI. Practitioners using blood flow reduction methods should be consistent with cuff use due to demonstrated differences across brands/widths. Equations using MAP and BMI appear best for prediction of leg LOP.

Stereo-EEG localization of midline onset seizures on scalp EEG.

PURPOSE: The objective of this study was to describe the sEEG-defined seizure onset zone (SOZ), seizure semiology, presurgical evaluations, surgical intervention and outcome in patients with midline onset noninvasive phase I monitoring. METHODS: A single center sEEG database was reviewed to identify patients with seizures onset predominantly involving midline electrodes (FZ, CZ, PZ, OZ) on scalp EEG. Data abstracted included clinical factors, seizure semiology graded into lobar segmentation, imaging and electrographic findings, sEEG plan, interventions, and outcome. RESULTS: Twelve patients were identified (8 males, median age of sEEG 28 years) out of 100 cases of sEEG performed from January 2015-September 2019. "Frontal lobe" seizure semiology was the most common. sEEG-defined SOZ were frontal (5), diffuse (1), multifocal (1), frontal and insular (1), frontal and cingulate (1), insular (1), cingulate (1), and mesial temporal (1). CZ and/or FZ scalp EEG changes were present for all patients with SOZ involving the frontal, cingulate, and insular regions. PZ/OZ scalp involvement was present in one patient with mesial temporal SOZ. Four patients underwent a definitive resective or ablative surgery, and the remaining patients underwent a palliative intervention. Of those with follow-up information available, 8/11 had seizure reduction by ≥ 50%, including 4 with an Engel I outcome. No clinical factors were associated with outcome. CONCLUSIONS: SOZ for midline onset seizures from noninvasive phase I monitoring was most commonly in the frontal, cingulate, and insular regions. A complex cortical network between these regions may explain overlap in semiology and scalp EEG findings. While the number rendered seizure-free was limited, a significant proportion experienced a reasonably favorable outcome justifying use of sEEG to identify surgical options in these patients.

Percutaneous Achilles Tendon Repair Using Ultrasound Guidance: An Intraoperative Ultrasound Technique.

Rupture of the Achilles tendon is a common injury seen in patients of varying ages and activity levels. There are many considerations for treatment of these injuries, with both operative and nonoperative management providing satisfactory outcomes in the literature. The decision to proceed with surgical intervention should be individualized for each patient, including the patient's age, future athletic goals, and comorbidities. Recently, a minimally invasive percutaneous approach to repair the Achilles tendon has been proposed as an equivalent alternative to the traditional open repair, while avoiding wound complications associated with larger incisions. However, many surgeons have been hesitant to adopt these approaches due to poor visualization, concern that suture capture in the tendon is not as robust, and the potential for iatrogenic sural nerve injury. The purpose of this Technical Note is to describe a technique using high-resolution ultrasound guidance intraoperatively during minimally invasive repair of the Achilles tendon. This technique minimizes the drawbacks of poor visualization associated with percutaneous repair, while providing the benefit of a minimally invasive approach.

Subclinical seizures on stereotactic EEG: characteristics and prognostic value.

OBJECTIVE: Although stereotactic EEG (sEEG) has become a widely used intracranial EEG technique, the significance of subclinical seizures (SCS) recorded on sEEG is unclear and studies examining this finding on sEEG are limited. We investigated (1) the prevalence of SCS in patients undergoing sEEG and clinical factors associated with their presence, (2) how often the subclinical seizure onset zone (SOZ) colocalizes with clinical SOZ, (3) the association of SCS and surgical outcomes, and (4) the influence of resection of the subclinical SOZ on surgical outcome. METHODS: We reviewed all patients who underwent intracranial monitoring with sEEG at our institution from 2015 through 2020 (n=169). Patient and seizure characteristics were recorded, as was concordance of subclinical and clinical seizures and post-surgical outcomes. RESULTS: SCS were observed during sEEG monitoring in 84 of 169 patients (50%). There was no difference in the prevalence of SCS based on imaging abnormalities, temporal vs extratemporal SOZ, number of electrodes, or pathology. SCS were more common in females than males (62% vs 40%, p=0.0054). SCS had complete concordance with clinical SOZ in 40% of patients, partial concordance in 29%, overlapping in 19%, and discordant in 12%. Eighty-three patients had surgery, 44 of whom had SCS. There was no difference in excellent outcome (ILAE 12 or 2) based on the presence of SCS or SCS concordance with clinical SOZ; however, there were improved outcomes in patients with complete resection of the subclinical SOZ compared with patients with incomplete resection (p =0.013). SIGNIFICANCE: These findings demonstrate that SCS are common during sEEG and colocalize with the clinical SOZ in most patients. Discordance with clinical SOZ does not necessarily predict poor surgical outcome; rather, complete surgical treatment of the subclinical SOZ correlates with excellent outcome. For unclear reasons, subclinical seizures occurred more commonly in females than males.

Non-alcoholic fatty liver disease (NAFLD) in Filipino North American patients: Results from a multi-ethnic cohort.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is more prevalent in certain ethnicities due to a combination of genetic, environmental, and metabolic factors. North American Filipino populations may have lifestyle and metabolic risk factors for NAFLD; however, the prevalence of NAFLD in this group is unknown. We sought to determine whether Filipino patients are over-represented in a multi-ethnic NAFLD cohort and describe their clinical presentation, primarily compared to other ethnicities in the same geographical region and secondarily compared to Manila-based Filipino patients. METHODS: A cross-sectional study was conducted with patients with NAFLD who were followed at the Hepatology Clinic at Vancouver General Hospital, Canada, from January 2015 to August 2018. Data were extracted for clinicodemographic data, ethnicity, anthropometric measures, blood work, and transient elastography (TE). External comparison data was obtained online from the Metro Vancouver census and a NAFLD study conducted in Manila, Philippines. RESULTS: Of 317 patients meeting inclusion criteria for the study, 224 patients had complete datasets. The mean age was 51.1 years, and 50% were female. There were 139 (62%) Caucasian and other ethnicity patients, 55 (25%) Asian patients, and 30 (13%) Filipino patients. Compared to other ethnic groups, the Filipino group had similar clinical characteristics, including NAFLD fibrosis scores and TE. Of included NAFLD patients, the proportion of Filipino patients (13.39%) was significantly greater than the proportion of Filipino residents in Metro Vancouver (5.52%, p <0.01). Our Filipino Canadians seemed to be younger, with fewer females and a lower proportion of diabetes mellitus, but a higher proportion of hypertension than the previously reported cohort from Manila. CONCLUSIONS: While Filipino patients have not previously been examined in multi-ethnic NAFLD studies, they may represent a high-risk population. Further research is needed to clarify the prevalence and presentation of NAFLD in Filipino Canadian patients, as this appears to be a significant health issue in this community.

Adolescent Baseball Pitchers With Ulnar Collateral Ligament Tears Exhibit a High Proportion of Partial Tears.

BACKGROUND: Ulnar collateral ligament (UCL) tears in the throwing elbow are classified according to grade and location using magnetic resonance arthrography (MRA). However, the frequency of each tear type and the association to age, competition level, and radiographic findings in adolescent baseball pitchers are unknown. PURPOSES: The primary purpose of this study was to use MRA to characterize the severity, location, and UCL tear type in adolescent pitchers. The second aim was to describe the relationship between the UCL tear type and age, competition level, and plain radiographic findings. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Records of adolescent pitchers with a UCL tear treated by the senior author between 2007 and 2016 were retrospectively reviewed. MRA scans were reviewed and tears were classified according to the Joyner-Andrews classification. Low-grade partial tears are classified as type I, high-grade partial tears as type II, complete full-thickness tears as type III, and tear pathology in >1 region in the UCL as type IV. Each type of tear also has a location designated at the midsubstance, ulna (U), or humerus (H). Patient characteristics, competition level, and associated plain radiographic abnormalities were recorded. Univariate analyses were performed to examine the relationships between tear types and age, competition level, and plain radiographic findings. RESULTS: A total of 200 adolescent pitchers (mean ± SD age, 17.2 ± 1.5 years) with MRA scans were reviewed. Type II-H (n = 62), type II-U (n = 51), and type III-U (n = 28) were the most common tear types observed. Type II tears comprised 64.5% of adolescent UCL tears, with type II-H being the most common. Plain radiographs were abnormal in 32% of patients, with calcifications (10.5%) and olecranon osteophytes (12.5%) being the most common findings. There were no significant relationships between tear type and age (P = .25), competition level (P = .23), or radiographic abnormalities (P = .75). CONCLUSION: Humeral-sided high-grade partial tears were the most common tear type in adolescent pitchers. There was no relationship between UCL tear type and age competition level, and plain radiographic abnormalities.

Validation of Monte Carlo 131 I radiopharmaceutical dosimetry workflow using a 3D-printed anthropomorphic head and neck phantom.

PURPOSE: Approximately 50% of head and neck cancer (HNC) patients will experience loco-regional disease recurrence following initial courses of therapy. Retreatment with external beam radiotherapy (EBRT) is technically challenging and may be associated with a significant risk of irreversible damage to normal tissues. Radiopharmaceutical therapy (RPT) is a potential method to treat recurrent HNC in conjunction with EBRT. Phantoms are used to calibrate and add quantification to nuclear medicine images, and anthropomorphic phantoms can account for both the geometrical and material composition of the head and neck. In this study, we present the creation of an anthropomorphic, head and neck, nuclear medicine phantom, and its characterization for the validation of a Monte Carlo, SPECT image-based, 131 I RPT dosimetry workflow. METHODS: 3D-printing techniques were used to create the anthropomorphic phantom from a patient CT dataset. Three 131 I SPECT/CT imaging studies were performed using a homogeneous, Jaszczak, and an anthropomorphic phantom to quantify the SPECT images using a GE Optima NM/CT 640 with a high energy general purpose collimator. The impact of collimator detector response (CDR) modeling and volume-based partial volume corrections (PVCs) upon the absorbed dose was calculated using an image-based, Geant4 Monte Carlo RPT dosimetry workflow and compared against a ground truth scenario. Finally, uncertainties were quantified in accordance with recent EANM guidelines. RESULTS: The 3D-printed anthropomorphic phantom was an accurate re-creation of patient anatomy including bone. The extrapolated Jaszczak recovery coefficients were greater than that of the 3D-printed insert (∼22.8 ml) for both the CDR and non-CDR cases (with CDR: 0.536 vs. 0.493, non-CDR: 0.445 vs. 0.426, respectively). Utilizing Jaszczak phantom PVCs, the absorbed dose was underpredicted by 0.7% and 4.9% without and with CDR, respectively. Utilizing anthropomorphic phantom recovery coefficient overpredicted the absorbed dose by 3% both with and without CDR. All dosimetry scenarios that incorporated PVC were within the calculated uncertainty of the activity. The uncertainties in the cumulative activity ranged from 23.6% to 106.4% for Jaszczak spheres ranging in volume from 0.5 to 16 ml. CONCLUSION: The accuracy of Monte Carlo-based dosimetry for 131 I RPT in HNC was validated with an anthropomorphic phantom. In this study, it was found that Jaszczak-based PVCs were sufficient. Future applications of the phantom could involve 3D printing and characterizing patient-specific volumes for more personalized RPT dosimetry estimates.

EEG source imaging concordance with intracranial EEG and epileptologist review in focal epilepsy.

EEG source imaging is becoming widely used for the evaluation of medically refractory focal epilepsy. The validity of EEG source imaging has been established in several studies comparing source imaging to the surgical resection cavity and subsequent seizure freedom. We present a cohort of 87 patients and compare EEG source imaging of both ictal and interictal scalp EEG to the seizure onset zone on intracranial EEG. Concordance of EEG source imaging with intracranial EEG was determined on a sublobar level and was quantified by measuring the distance between the source imaging result and the centroid of the active seizure onset zone electrodes. The EEG source imaging results of a subgroup of 26 patients with high density 76-channel EEG were compared with the localization of three experienced epileptologists. Of 87 patients, 95% had at least one analysis concordant with intracranial EEG and 74% had complete concordance. There was a higher rate of complete concordance in temporal lobe epilepsy compared to extratemporal (89.3 and 62.8%, respectively, P = 0.015). Of the total 282 analyses performed on this cohort, higher concordance was also seen in temporal discharges (95%) compared to extratemporal (77%) (P = 0.0012), but no difference was seen comparing high-density EEG with standard (32-channel) EEG. Subgroup analysis of ictal waveforms showed greater concordance for ictal spiking, compared with rhythmic activity, paroxysmal fast activity, or obscured onset. Median distances from the dipole and maximum distributed source to a centroid of seizure onset zone electrodes were 30.0 and 32.5 mm, respectively, and the median distances from dipole and maximum distributed source to nearest seizure onset zone electrode were 22.8 and 21.7, respectively. There were significantly shorter distances in ictal spiking. There were shorter distances in patients with Engel Class 1 outcome from surgical resection compared to patients with worse outcomes. For the subgroup of 26 high-density EEG patients, EEG source localization had a significantly higher concordance (92% versus 65%), sensitivity (57% versus 35%) and positive predictive value (60% versus 36%) compared with epileptologist localization. Our study demonstrates good concordance between ictal and interictal source imaging and intracranial EEG. Temporal lobe discharges have higher concordance rates than extratemporal discharges. Importantly, this study shows that source imaging has greater agreement with intracranial EEG than visual review alone, supporting its role in surgical planning.

A United States Fair Lending Perspective on Machine Learning.

The use of machine learning (ML) has become more widespread in many areas of consumer financial services, including credit underwriting and pricing of loans. ML's ability to automatically learn nonlinearities and interactions in training data is perceived to facilitate faster and more accurate credit decisions, and ML is now a viable challenger to traditional credit modeling methodologies. In this mini review, we further the discussion of ML in consumer finance by proposing uniform definitions of key ML and legal concepts related to discrimination and interpretability. We use the United States legal and regulatory environment as a foundation to add critical context to the broader discussion of relevant, substantial, and novel ML methodologies in credit underwriting, and we review numerous strategies to mitigate the many potential adverse implications of ML in consumer finance.

Hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging of Pyruvate Metabolism in Murine Breast Cancer Models of Different Metastatic Potential.

This study uses dynamic hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) to estimate differences in glycolytic metabolism between highly metastatic (4T1, n = 7) and metastatically dormant (4T07, n = 7) murine breast cancer models. The apparent conversion rate of pyruvate-to-lactate (kPL) and lactate-to-pyruvate area-under-the-curve ratio (AUCL/P) were estimated from the metabolite images and compared with biochemical metabolic measures and immunohistochemistry (IHC). A non-significant trend of increasing kPL (p = 0.17) and AUCL/P (p = 0.11) from 4T07 to 4T1 tumors was observed. No significant differences in tumor IHC lactate dehydrogenase-A (LDHA), monocarboxylate transporter-1 (MCT1), cluster of differentiation 31 (CD31), and hypoxia inducible factor-α (HIF-1α), tumor lactate-dehydrogenase (LDH) activity, or blood lactate or glucose levels were found between the two tumor lines. However, AUCL/P was significantly correlated with tumor LDH activity (ρspearman = 0.621, p = 0.027) and blood glucose levels (ρspearman = -0.474, p = 0.042). kPL displayed a similar, non-significant trend for LDH activity (ρspearman = 0.480, p = 0.114) and blood glucose levels (ρspearman = -0.414, p = 0.088). Neither kPL nor AUCL/P were significantly correlated with blood lactate levels or tumor LDHA or MCT1. The significant positive correlation between AUCL/P and tumor LDH activity indicates the potential of AUCL/P as a biomarker of glycolytic metabolism in breast cancer models. However, the lack of a significant difference between in vivo tumor metabolism for the two models suggest similar pyruvate-to-lactate conversion despite differing metastatic potential.

A device for the controlled cooling and freezing of excised plant specimens during magnetic resonance imaging.

BACKGROUND: Investigating plant mechanisms to tolerate freezing temperatures is critical to developing crops with superior cold hardiness. However, the lack of imaging methods that allow the visualization of freezing events in complex plant tissues remains a key limitation. Magnetic resonance imaging (MRI) has been successfully used to study many different plant models, including the study of in vivo changes during freezing. However, despite its benefits and past successes, the use of MRI in plant sciences remains low, likely due to limited access, high costs, and associated engineering challenges, such as keeping samples frozen for cold hardiness studies. To address this latter need, a novel device for keeping plant specimens at freezing temperatures during MRI is described. RESULTS: The device consists of commercial and custom parts. All custom parts were 3D printed and made available as open source to increase accessibility to research groups who wish to reproduce or iterate on this work. Calibration tests documented that, upon temperature equilibration for a given experimental temperature, conditions between the circulating coolant bath and inside the device seated within the bore of the magnet varied by less than 0.1 °C. The device was tested on plant material by imaging buds from Vaccinium macrocarpon in a small animal MRI system, at four temperatures, 20 °C, - 7 °C, - 14 °C, and - 21 °C. Results were compared to those obtained by independent controlled freezing test (CFT) evaluations. Non-damaging freezing events in inner bud structures were detected from the imaging data collected using this device, phenomena that are undetectable using CFT. CONCLUSIONS: The use of this novel cooling and freezing device in conjunction with MRI facilitated the detection of freezing events in intact plant tissues through the observation of the presence and absence of water in liquid state. The device represents an important addition to plant imaging tools currently available to researchers. Furthermore, its open-source and customizable design ensures that it will be accessible to a wide range of researchers and applications.

Evaluating the effectiveness of a lower extremity venous phantom on developing ultrasound examination skills and confidence.

INTRODUCTION: The aims of this study were: (1) Determine the effect on student ultrasound scanning skills using a lower extremity venous ultrasound phantom in addition to standard teaching methods of didactic lecture and scanning live volunteers and (2) Determine the effect of using a lower extremity venous ultrasound phantom in addition to standard teaching methods of didactic lecture and scanning live volunteers on student confidence levels in performing the lower extremity venous ultrasound examination. METHODS: Participants were first year diagnostic medical sonography students with minimal scanning experience (n = 11), which were randomized into two groups. Group 1 (n = 5) received the standard didactic lecture and attended a scan lab assessment where they performed a lower extremity venous examination on a human volunteer. Group 2 (n = 6) received the standard didactic lecture, performed three scheduled scanning sessions on an anatomic lower extremity venous phantom with flow and then attended the same scan lab assessment as Group 1, where they performed a lower extremity venous examination on a human volunteer. RESULTS: Scan lab assessments on day 4 of the study demonstrated a significant difference in scanning performance (p = 0.019) between the two groups. Post scan lab assessment confidence scores also demonstrated a significant difference between how participants in each group scored their confidence levels (p = 0.0260), especially in the ability to image calf veins. CONCLUSIONS: This study suggests anatomical phantoms can be used to develop scanning skills and build confidence in ultrasound imaging of the lower extremity venous structures.

Measurement of the temperature-dependent output of lead zirconate titanate transducers.

The effect of temperature and electrical drive conditions on the output of lead zirconate titanate (PZT) transducers is of particular interest in ultrasound metrology and medical ultrasound applications. In this work, the temperature-dependent output of two single-element PZT transducers was measured between 22 °C and 46 °C. Two independent measurement methods were used, namely radiation force balance measurements and laser vibrometry. When driven at constant voltage using a 50 Ω matched signal generator and amplifier using continuous wave (CW) or quasi-CW excitation, the output of the two transducers increased on average by 0.6 % per degree, largely due to an increase in transducer efficiency with temperature. The two measurement methods showed close agreement. Similar trends were observed when using single cycle excitation with the same signal chain. However, when driven using a pulser (which is not electrically matched), the two transducers exhibited different behaviour depending on their electrical impedance. Accounting for the temperature-dependent output of PZT transducers could have implications for many areas of ultrasound metrology, for example, in therapeutic ultrasound where a coupling fluid at an increased or decreased temperature is often used.

Ultrasound mediated delivery of quantum dots from a proof of concept capsule endoscope to the gastrointestinal wall.

Biologic drugs, defined as therapeutic agents produced from or containing components of a living organism, are of growing importance to the pharmaceutical industry. Though oral delivery of medicine is convenient, biologics require invasive injections because of their poor bioavailability via oral routes. Delivery of biologics to the small intestine using electronic delivery with devices that are similar to capsule endoscopes is a promising means of overcoming this limitation and does not require reformulation of the therapeutic agent. The efficacy of such capsule devices for drug delivery could be further improved by increasing the permeability of the intestinal tract lining with an integrated ultrasound transducer to increase uptake. This paper describes a novel proof of concept capsule device capable of electronic application of focused ultrasound and delivery of therapeutic agents. Fluorescent markers, which were chosen as a model drug, were used to demonstrate in vivo delivery in the porcine small intestine with this capsule. We show that the fluorescent markers can penetrate the mucus layer of the small intestine at low acoustic powers when combining microbubbles with focused ultrasound during in vivo experiments using porcine models. This study illustrates how such a device could be potentially used for gastrointestinal drug delivery and the challenges to be overcome before focused ultrasound and microbubbles could be used with this device for the oral delivery of biologic therapeutics.

A Learning-Based Microultrasound System for the Detection of Inflammation of the Gastrointestinal Tract.

Inflammation of the gastrointestinal (GI) tract accompanies several diseases, including Crohn's disease. Currently, video capsule endoscopy and deep bowel enteroscopy are the main means for direct visualisation of the bowel surface. However, the use of optical imaging limits visualisation to the luminal surface only, which makes early-stage diagnosis difficult. In this study, we propose a learning enabled microultrasound ( µ US) system that aims to classify inflamed and non-inflamed bowel tissues. µ US images of the caecum, small bowel and colon were obtained from mice treated with agents to induce inflammation. Those images were then used to train three deep learning networks and to provide a ground truth of inflammation status. The classification accuracy was evaluated using 10-fold evaluation and additional B-scan images. Our deep learning approach allowed robust differentiation between healthy tissue and tissue with early signs of inflammation that is not detectable by current endoscopic methods or by human inspection of the µ US images. The methods may be a foundation for future early GI disease diagnosis and enhanced management with computer-aided imaging.

Modeling early thermal injury using an ex vivo human skin model of contact burns.

BACKGROUND: Early mechanisms underlying the progressive tissue death and the regenerative capability of burn wounds are understudied in human skin. A clinically relevant, reproducible model for human burn wound healing is needed to elucidate the early changes in the human burn wound environment. This study reports a reproducible contact burn model on human skin that explores the extent of tissue injury and healing over time, and defines the inter-individual variability in human skin to enable use in mechanistic studies on burn wound progression and healing. METHODS: Using a customized burn device, contact burns of various depths were created on human skin by two operators and were evaluated for histologic depth by three raters to determine reproducibility. Early burn wound progression and wound healing were also evaluated histologically after the thermally injured human skin was cultured ex vivo for up to 14 days. RESULTS: Burn depths were reproducibly generated on human skin in a temperature- or time-dependent manner. No significant difference in operator-created or rater-determined depth was observed within each patient sample. However, significant inter-individual variation was identified in burn depth in ten patient samples. Burn-injured ex vivo human skin placed into culture demonstrated differential progression of cell death and collagen denaturation for high and low temperature contact burns, while re-epithelialization was observed in superficial burn wounds over a period of 14 days. CONCLUSION: This model represents an invaluable tool to evaluate the inter-individual variability in early burn wound progression and wound healing to complement current animal models and enhance the translation of preclinical research to improvements in patient care.