Name: a novel non-invasive method for the detection of elevated intra-compartmental pressures of the leg
Uploaded: 2019-05-31T15:00:00
Description: Watch this Scientific Journal Video about A Novel Non-invasive Method for the Detection of Elevated Intra-compartmental Pressures of the Leg at JoVE.com

This experimental protocol has been reviewed and approved by our hospital&#8217;s institutional review board (IRB) and follows all guidelines set forth by our institution&#8217;s human research ethics committee.
1. Identify the Fascia of the Anterior Compartment of the Leg
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	<li>Identify a starting site for the ultrasound probe. Place the probe directly over the anterior compartment, just lateral to the tibial crest and one handbreadth distal to the tibial tubercle.</li>
	<li>Identify th...

<ol>
	<li>Ulmer, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+clinical+diagnosis+of+compartment+syndrome+of+the+lower+leg:+are+clinical+findings+predictive+of+the+disorder?.">The clinical diagnosis of compartment syndrome of the lower leg: are clinical findings predictive of the disorder?.</a> Journal of Orthopaedic Trauma. 16 (8), 572-577 (2002).</li><li>Whitesides, T. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tissue+pressure+measurements+as+a+determinant+for+the+need+of+fasciotomy.">Tissue pressure measurements as a determinant for the need of fasciotomy.</a> Clinical Orthopaedics and Related Research. 113, 43-51 (1975).</li><li>McQueen, M. M., Court-Brown, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Compartment+monitoring+in+tibial+fractures:+the+pressure+threshold+for+decompression.">Compartment monitoring in tibial fractures: the pressure threshold for decompression.</a> The Journal of Bone and Joint Surgery. British Volume. 78 (1), 99-104 (1996).</li><li>McQueen, M. M., Christie, J., Court-Brown, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Compartment+pressures+after+intramedullary+nailing+of+the+tibia.">Compartment pressures after intramedullary nailing of the tibia.</a> The Journal of Bone and Joint Surgery. British Volume. 72 (3), 395-397 (1990).</li><li>Masquelet, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+compartment+syndrome+of+the+leg:+pressure+measurement+and+fasciotomy.">Acute compartment syndrome of the leg: pressure measurement and fasciotomy.</a> Orthopaedics &amp; Traumatology: Surgery &amp; Research. 96 (8), 913-917 (2010).</li><li>McQueen, M. M., Duckworth, A. D., Aitken, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+estimated+sensitivity+and+specificity+of+compartment+pressure+monitoring+for+acute+compartment+syndrome.">The estimated sensitivity and specificity of compartment pressure monitoring for acute compartment syndrome.</a> Journal of Bone and Joint Surgery. 95 (8), 673-677 (2013).</li><li>Whitney, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Do+one-time+intracompartmental+pressure+measurements+have+a+high+false-positive+rate+in+diagnosing+compartment+syndrome?.">Do one-time intracompartmental pressure measurements have a high false-positive rate in diagnosing compartment syndrome?.</a> Journal of Trauma and Acute Care Surgery. 76 (2), 479-483 (2014).</li><li>Sellei, R. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+elevated+compartment+pressures+by+pressure-related+ultrasound:+a+cadaveric+model.">Assessment of elevated compartment pressures by pressure-related ultrasound: a cadaveric model.</a> European Journal of Trauma and Emergency Surgery. 41 (6), 639-645 (2015).</li><li>Sellei, R. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Compartment+elasticity+measured+by+pressure-related+ultrasound+to+determine+patients+&#8220;at+risk&#8221;+for+compartment+syndrome:+an+experimental+in+vitro+study.">Compartment elasticity measured by pressure-related ultrasound to determine patients &#8220;at risk&#8221; for compartment syndrome: an experimental in vitro study.</a> Patient Safety in Surgery. 9 (1), 4 (2015).</li><li>Bloch, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Compression+sonography+for+non-invasive+measurement+of+lower+leg+compartment+pressure+in+an+animal+model.&amp;#34;.">Compression sonography for non-invasive measurement of lower leg compartment pressure in an animal model.&amp;#34;.</a> Injury. 49 (3), 532-537 (2018).</li><li>Marmor, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+standard+musculoskeletal+ultrasound+to+determine+the+need+for+fasciotomy+in+an+elevated+muscle+compartment+pressure+cadaver+leg+model.">Use of standard musculoskeletal ultrasound to determine the need for fasciotomy in an elevated muscle compartment pressure cadaver leg model.</a> Injury. , (2019).</li></ol>

This article demonstrates a novel, clinically applicable technique for the non-invasive measurement of intra-compartmental pressures in the leg using an ultrasound coupled with a pressure sensor. This technique only requires a hand-held ultrasound and a commercially available pressure sensing transducer. It is quick and easy to perform and is well tolerated by patients. The entire diagnostic procedure can be performed in under 5 min with no additional resources. The calculated delta CFFP may then be used in conjunction w...

The purpose of this novel protocol is to evaluate the intra-compartmental pressure of the leg in a non-invasive way by using an ultrasound transducer coupled with a pressure sensor. Compartment syndrome is a well-known complication in musculoskeletal trauma and is the result of elevated intra-compartmental pressures which compromise the perfusion of tissues leading to irreversible ischemic injury if not intervened upon. Its diagnosis is primarily based on clinical exam. Unfortunately, clinical exam alone has been shown to have poor sensitivity and specificity in the diagnosis of compartment syndrome1. Invasive intra-compartmental pressure measuring by needle manometry is commonly used in the assessment of compartment syndrome2,3,4. The disadvantage of needle manometry is that it is an invasive procedure, being quite uncomfortable for the patient and not amenable to serial measurements. Furthermore, invasive intra-compartmental pressure measuring measurement is not routinely performed by some surgeons due to considerable disagreement over the appropriate threshold pressure for diagnosis of ACS and the high (35%) false positive rate and variability of a single invasive measurement5,6,7.
It has been previously demonstrated in artificial, animal, and human cadaver models that a rise in the intra-compartmental pressure results in a decreased elasticity of the fascia overlying the anterior compartment suggesting a correlation between the intra-compartmental pressure and compliance of the facial compartment as measured by ultrasound8,9,10. Further work has described using the pressure required to flatten the fascia of the anterior compartment as measured by ultrasound (Compartment Fascia Flattening Pressure [CFFP]) as a surrogate measure of the intra-compartmental pressure11. The anterior compartment fascia can be readily visualized with standard ultrasonography and, with the addition of a pressure sensor to the probe, CFFPs can be easily and reliably measured. This protocol offers a non-invasive diagnostic alternative for evaluating intra-compartmental pressures and can be performed quickly and serially with little to no patient discomfort.

<table>
<tbody>
<tr>
<td>Pressure sensor: Venous pressure measurement device</td>
<td>Vein press</td>
<td>VP 2014</td>
<td>A peripheral venous measuring device used in conjuction with an ultrasound to measure peripheral venous pressure.</td>
</tr>
<tr>
<td>Ultrasound probe: Vscan Extend R2 Dual Probe DICOM Base Package</td>
<td>GE Healthcare</td>
<td>H8038VP</td>
<td>Any ultrasound probe will be sufficent for this test. Using the narrow tranducer will function best when coupled to the pressure sensor</td>
</tr>
</tbody>
</table>

a novel non-invasive method for the detection of elevated intra-compartmental pressures of the leg

Acute Compartment Syndrome is a devastating consequence of musculoskeletal trauma. Currently the diagnosis is based on clinical signs and symptoms, and while adjuncts such as invasive intra-compartmental pressure measurements are often used to corroborate the physical exam findings, there remains no reliable objective test to aid in the decision to perform a decompressive fasciotomy. In a cadaver model of compartment syndrome, an ultrasound (US) based method has been shown to be a reliable measurement of increased intra-compartmental pressure. An absolute pressure of &#62;100 mbar or a difference of 50 mbar in the CFFP between the legs can be considered pathologic. Using an ultrasound transducer, coupled with a pressure sensor, the pressure needed to flatten the superficial fascia of the anterior compartment of lower legs (Compartment Fascia Flattening Pressure [CFFP]) can be measured. The CFFP of the injured leg is compared to the CFFP of the uninjured leg. This US measured index can then serve as an adjunct to the physical exam in evaluating injured lower extremities and assessing the need for decompressive fasciotomy. The advantages of this protocol include: being a non-invasive method and an easily reproducible technique.

This technique has been used to measure 10 consecutive patients with injured legs without evidence of compartment syndrome and 3 patients with a clinical diagnosis of compartment syndrome necessitating decompressive fasciotomies. The average delta CFFP for patients without compartment syndrome was 10.7 &#177; 10.6 mbar compared to 157 &#177; 51.7 mbar for patients with compartment syndrome and single-tailed t-test identified the differences in pressures between the groups as being statistically significant (P &#60; 0.02)...

Watch this Scientific Journal Video about A Novel Non-invasive Method for the Detection of Elevated Intra-compartmental Pressures of the Leg at JoVE.com

A Novel Non-invasive Method for the Detection of Elevated Intra-compartmental Pressures of the Leg

An ultrasound probe coupled with a pressure sensor is used to assess the intra-compartmental pressure of the leg by directly measuring the compartment fascia flattening pressure (CFFP). This non-invasive protocol will provide reliable assessment of the pressure inside the anterior muscular compartment of the lower leg.

Acute Compartment Syndrome is a devastating consequence of musculoskeletal trauma. Currently the diagnosis is based on clinical signs and symptoms, and ...

This protocol is uniquely significant because it's a non-invasive means of assessing intra-compartmental pressures in the leg. This can be important when evaluating an injured extremity, which may be at risk for compartment syndrome, a limb-threatening condition. As intra-compartmental pressures rise, the perfusion of the structures within the compartment decreases, leading to an ischemic insult.If elevated pressures are not identified and treated quickly, the compartment dies, resulting in permanent disability. The primary advantage of this technique is its non-invasiveness. Currently, the only means by which to measure intra-compartmental pressure is by inserting a large-bore needle equipped with a pressure gauge into the leg compartment.While reliable, this technique is quite uncomfortable to the patient and is not suitable for performing serial measurements. For someone first trying this technique, I would recommend that they first practice the technique on a volunteer. Learning the amount of pressure to apply and interpreting the ultrasound images can be difficult at first.To begin this procedure, identify a starting site for the ultrasound probe. Place the probe directly over the anterior compartment, just lateral to the tibial crest and one hand breadth distal to the tibial tubercle. Next, identify the fascia, which is the bright white strip just below the subcutaneous tissue on the ultrasound.Move the probe until the fascia is seen at the point where it attaches to the tibial crest. Note the geometry of the fascia. With minimal applied, this should be a convex shape.Once the fascia of the anterior compartment is identified, apply slow and steady pressure to the ultrasound probe until the fascia changes shape from convex to completely flat. Make several attempts, including passing the flattening point to produce a concave shape in an effort to gently hone in on the exact compartment fascia flattening pressure. Once the anterior compartment fascia is perfectly flat, record the pressure sensor measurement.Repeat the CFFP measurement two more times. Record an average, all three pressures, to define the final CFFP of the injured leg. First, measure and record the CFFP in the contralateral leg in the same manner previously described.Calculate the delta CFFP by taking the difference between the CFFP of the injured leg from the CFFP of the well leg. In this study, a novel, clinically applicable technique for the non-invasive measurement of intra-compartmental pressures in the leg is demonstrated using an ultrasound coupled with a pressure sensor. This technique has been used to measure 10 consecutive patients with injured legs without evidence of compartment syndrome, and three patients with a clinical diagnosis of compartment syndrome, necessitating decompressive fasciotomies.The average delta CFFP for patients without compartment syndrome is approximately 10.7 millibar, compared to approximately 157 millibar for patients with compartment syndrome. A single-tailed T-test identified the differences in pressures between the groups as being statistically significant. When performing this technique, it is important to identify the pressure at the exact point when the fascia changes from convex to completely flat.To best facilitate this, it is helpful to have an assistant available to read the pressure while the person performing the technique maintains their focus on the ultrasound. Once the fascia changes from convex to flat, the person performing the test can call out pressure, signaling the assistant to record the pressure reading. After this diagnostic test is performed, the results can be compared against the gold standard for assessing intra-compartmental pressures, which is needle manometry.The most commonly used device for this is the Stryker quick pressure monitor set.

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High-frequency High-resolution Echocardiography: First Evidence on Non-invasive Repeated Measure of Myocardial Strain, Contractility, and Mitral Regurgitation in the Ischemia-reperfused Murine Heart

Ischemia-reperfusion (IR) was surgically performed in murine hearts which were then subjected to repeated imaging to monitor temporal changes in functional parameters of key clinical significance. Two-dimensional movies were acquired at high frame rate (8 kHz) and were utilized to estimate high-quality myocardial strain. Two-dimensional elastograms (strain images), as well as strain profiles, were visualized. Results were powerful in quantitatively assessing IR-induced changes in cardiac events including left-ventricular (LV) contraction, LV relaxation and isovolumetric phases of both pre-IR and post-IR beating hearts in intact mice. In addition, compromised sector-wise wall motion and anatomical deformation in the infarcted myocardium were visualized.  The elastograms were uniquely able to provide information on the following parameters in addition to standard physiological indices that are known to be affected by myocardial infarction in the mouse: internal diameters of mitral valve orifice and aorta, effective regurgitant orifice, myocardial strain (circumferential as well as radial), turbulence in blood flow pattern as revealed by the color Doppler movies and velocity profiles, asynchrony in LV sector, and changes in the length and direction of vectors demonstrating slower and asymmetrical wall movement. This work emphasizes on the visual demonstration of how such analyses are performed. 

High-frequency High-resolution Echocardiography: First Evidence on Non-invasive Repeated Measure of Myocardial Strain, Contractility, and Mitral Regurgitation in the Ischemia-reperfused Murine Heart 

High frequency Doppler ultrasound is a novel technology for assessing regional myocardial function. This work presents first evidence demonstrating applicability of this versatile imaging platform for the repeated measure of myocardial strain, dp/dt, and mitral regurgitation in the ischemia-reperfused (IR) murine heart.

Ischemia-reperfusion (IR) was surgically performed in murine hearts which were then subjected to repeated imaging to monitor temporal changes in ...

A Method for Murine Islet Isolation and Subcapsular Kidney Transplantation

Since the early pioneering work of Ballinger and Reckard demonstrating that transplantation of islets of Langerhans into diabetic rodents could normalize their blood glucose levels, islet transplantation has been proposed to be a potential treatment for type 1 diabetes 1,2. More recently, advances in human islet transplantation have further strengthened this view 1,3. However, two major limitations prevent islet transplantation from being a widespread clinical reality: (a) the requirement for large numbers of islets per patient, which severely reduces the number of potential recipients, and (b) the need for heavy immunosuppression, which significantly affects the pediatric population of patients due to their vulnerability to long-term immunosuppression. Strategies that can overcome these limitations have the potential to enhance the therapeutic utility of islet transplantation.
Islet transplantation under the mouse kidney capsule is a widely accepted model to investigate various strategies to improve islet transplantation. This experiment requires the isolation of high quality islets and implantation of islets to the diabetic recipients. Both procedures require surgical steps that can be better demonstrated by video than by text. Here, we document the detailed steps for these procedures by both video and written protocol. We also briefly discuss different transplantation models: syngeneic, allogeneic, syngeneic autoimmune, and allogeneic autoimmune.

Transplantation of isolated islets has been proposed to be a potential treatment for type 1 diabetes. Here we describe a method to isolate islets from mouse pancreata and transplant them to the subcapsular space of the kidney.

Since the early pioneering work of Ballinger and Reckard demonstrating that transplantation of islets of Langerhans into diabetic rodents could normalize ...

Corneal Confocal Microscopy: A Novel Non-invasive Technique to Quantify Small Fibre Pathology in Peripheral Neuropathies

The accurate quantification of peripheral neuropathy is important to define at risk patients, anticipate deterioration, and assess new therapies. Conventional methods assess neurological deficits and electrophysiology and quantitative sensory testing quantifies functional alterations to detect neuropathy. However, the earliest damage appears to be to the small fibres and yet these tests primarily assess large fibre dysfunction and have a limited ability to demonstrate regeneration and repair. The only techniques which allow a direct examination of unmyelinated nerve fibre damage and repair are sural nerve biopsy with electron microscopy and skin-punch biopsy. However, both are invasive procedures and require lengthy laboratory procedures and considerable expertise. Corneal Confocal microscopy is a non-invasive clinical technique which provides in-vivo imaging of corneal nerve fibres. We have demonstrated early nerve damage, which precedes loss of intraepidermal nerve fibres in skin biopsies together with stratification of neuropathic severity and repair following pancreas transplantation in diabetic patients. We have also demonstrated nerve damage in idiopathic small fibre neuropathy and Fabry's disease.

Corneal Confocal microscopy is a non-invasive clinical technique which may be used to quantify C fibre damage to diagnose and stratify patients with increasing neuropathic severity.

The accurate quantification of peripheral neuropathy is important to define at risk patients, anticipate deterioration, and assess new therapies. ...

Method for Novel Anti-Cancer Drug Development using Tumor Explants of Surgical Specimens

The current therapies for malignant glioma have only palliative effect. For therapeutic development, one hurdle is the discrepancy of efficacy determined by current drug efficacy tests and the efficacy on patients. Thus, novel and reliable methods for evaluating drug efficacy are warranted in pre-clinical phase. In vitro culture of tumor tissues, including cell lines, has substantial phenotypic, genetic, and epigenetic alterations of cancer cells caused by artificial environment of cell culture, which may not reflect the biology of original tumors in situ. Xenograft models with the immunodeficient mice also have limitations, i.e., the lack of immune system and interspecies genetic and epigenetic discrepancies in microenvironment. Here, we demonstrate a novel method using the surgical specimens of malignant glioma as undissociated tumor blocks to evaluate treatment effects. To validate this method, data with the current first-line chemotherapeutic agent, temozolomide (TMZ), are described.


We used the freshly-removed surgical specimen of malignant glioma for our experiments. We performed intratumoral injection of TMZ or other drug candidates, followed by incubation and analysis on surgical specimens. Here, we sought to establish a tumor tissue explant method as a platform to determine the efficacy of novel anti-cancer therapies so that we may be able to overcome, at least, some of the current limitations and fill the existing gap between the current experimental data and the efficacy on an actual patient's tumor. This method may have the potential to accelerate identifying novel chemotherapeutic agents for solid cancer treatment.

Here, we established a method for drug efficacy testing with surgical specimens of brain tumors, termed &#x201C;tumor explant method&#x201D;. With this method, we can evaluate drug efficacy without breaking the microenvironment of solid tumors. To validate reliability of this method, we describe representative data with our glioma specimen treated with the current first-line chemotherapeutic agent, temozolomide.


The current therapies for malignant glioma have only palliative effect. For therapeutic development, one hurdle is the discrepancy of efficacy determined ...

Use of Animal Model of Sepsis to Evaluate Novel Herbal Therapies

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several techniques, including infusion of exogenous bacterial toxin (endotoxemia) or bacteria (bacteremia), as well as surgical perforation of the cecum by cecal ligation and puncture (CLP)1-3. CLP allows bacteria spillage and fecal contamination of the peritoneal cavity, mimicking the human clinical disease of perforated appendicitis or diverticulitis. The severity of sepsis, as reflected by the eventual mortality rates, can be controlled surgically by varying the size of the needle used for cecal puncture2. In animals, CLP induces similar, biphasic hemodynamic cardiovascular, metabolic, and immunological responses as observed during the clinical course of human sepsis3. Thus, the CLP model is considered as one of the most clinically relevant models for experimental sepsis1-3.
Various animal models have been used to elucidate the intricate mechanisms underlying the pathogenesis of experimental sepsis. The lethal consequence of sepsis is attributable partly to an excessive accumulation of early cytokines (such as TNF, IL-1 and IFN-&gamma;)4-6 and late proinflammatory mediators (e.g., HMGB1)7. Compared with early proinflammatory cytokines, late-acting mediators have a wider therapeutic window for clinical applications. For instance, delayed administration of HMGB1-neutralizing antibodies beginning 24 hours after CLP, still rescued mice from lethality8,9, establishing HMGB1 as a late mediator of lethal sepsis. The discovery of HMGB1 as a late-acting mediator has initiated a new field of investigation for the development of sepsis therapies using Traditional Chinese Herbal Medicine. In this paper, we describe a procedure of CLP-induced sepsis, and its usage in screening herbal medicine for HMGB1-targeting therapies.

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection, and can be simulated by a surgical technique termed cecal ligation and puncture (CLP). Here we describe a method to use CLP-induced animal model to screen medicinal herbs for therapeutic agents.

Sepsis refers to a systemic inflammatory response syndrome resulting from a microbial infection. It has been routinely simulated in animals by several ...

Intraoperative Detection of Subtle Endometriosis: A Novel Paradigm for Detection and Treatment of Pelvic Pain Associated with the Loss of Peritoneal Integrity

Endometriosis is a common disease affecting 40 to 70% of reproductive-aged women with chronic pelvic pain (CPP) and/or infertility. The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surfaces during laparoscopy (L/S) to detect the loss of peritoneal integrity in patients with pelvic pain and suspected endometriosis. Forty women with CPP and 5 women without pain were evaluated in this pilot study. During L/S, concentrated dye was sprayed onto peritoneal surfaces, then aspirated and rinsed with Lactated Ringers solution. Areas of localized dye uptake were evaluated for the presence of visible endometriotic lesions. Areas of intense peritoneal staining were resected and some fixed in 2.5% buffered gluteraldehyde and examined by scanning (SEM) electron microscopy. Blue dye uptake was more common in women with endometriosis and chronic pelvic pain than controls (85% vs. 40%). Resection of the blue stained areas revealed endometriosis by SEM and loss of peritoneal cell-cell contact compared to normal, non-staining peritoneum. Affected peritoneum was associated with visible endometriotic implants in most but not all patients. Subjective pain relief was reported in 80% of subjects. Based on scanning electron microscopy, we conclude that endometrial cells extend well beyond visible implants of endometriosis and appear to disrupt the underlying mesothelium. Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity, allowing menstrual or ovulatory blood and associated pain factors access to underlying sensory nerves. Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP. This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at L/S and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy.

Loss of peritoneal integrity provides a new paradigm to understand and treat chronic pelvic pain in women with mild forms of endometriosis and can be easily detected using intraoperative instillation of dye at the time of laparoscopy.

Endometriosis is a  common disease affecting 40 to 70% of reproductive-aged women with chronic  pelvic pain (CPP) and/or infertility. The purpose of this ...

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality and morbidity, but there is not yet an effective bedside tool that can accurately screen for brain injury, monitor injury evolution, or assess response to therapy. The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO2). Thus, measures of CMRO2 are reflective of neuronal viability and provide critical diagnostic information, making CMRO2 an ideal target for bedside measurement of brain health.
Brain-imaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) yield measures of cerebral glucose and oxygen metabolism, but these techniques require the administration of radionucleotides, so they are used in only the most acute cases.
Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO2) as a surrogate for cerebral oxygen consumption. However, SO2 is less than ideal as a surrogate for cerebral oxygen metabolism as it is influenced by both oxygen delivery and consumption. Furthermore, measurements of SO2 are not sensitive enough to detect brain injury hours after the insult 1,2, because oxygen consumption and delivery reach equilibrium after acute transients 3. We investigated the possibility of using more sophisticated NIRS optical methods to quantify cerebral oxygen metabolism at the bedside in healthy and brain-injured newborns. More specifically, we combined the frequency-domain NIRS (FDNIRS) measure of SO2 with the diffuse correlation spectroscopy (DCS) measure of blood flow index (CBFi) to yield an index of CMRO2 (CMRO2i) 4,5.
With the combined FDNIRS/DCS system we are able to quantify cerebral metabolism and hemodynamics. This represents an improvement over CWNIRS for detecting brain health, brain development, and response to therapy in neonates. Moreover, this method adheres to all neonatal intensive care unit (NICU) policies on infection control and institutional policies on laser safety. Future work will seek to integrate the two instruments to reduce acquisition time at the bedside and to implement real-time feedback on data quality to reduce the rate of data rejection.

We combined frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation with diffuse correlation spectroscopy measures of cerebral blood flow index to estimate an index of oxygen metabolism. We tested the utility of this measure as a bedside screening tool to evaluate the health and development of the newborn brain.

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic mechanisms that contribute to the onset and progression of intestinal diseases. The identification of new molecules that promote these pathologies has led to a flurry of activity focused on the development of potential new therapies to inhibit their function. As a result, various pre-clinical mouse models with an intact immune system and stromal microenvironment are now heavily used. Here we describe three experimental protocols to test the efficacy of new therapeutics in pre-clinical models of (1) acute mucosal damage, (2) chronic colitis and/or colitis-associated colon cancer, and (3) sporadic colorectal cancer. We also outline procedures for serial endoscopic examination that can be used to document the therapeutic response of an individual tumor and to monitor the health of individual mice. These protocols provide complementary experimental platforms to test the effectiveness of therapeutic compounds shown to be well tolerated by mice.

We describe methods for longitudinal monitoring of the efficacy of therapeutics for the treatment of colonic pathologies in mice using a rigid endoscope. This protocol can be readily used for the characterization of the therapeutic response of an individual tumor in live mice and also for monitoring potential disease relapse.

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic ...

Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases

3-[18F]fluoro-4-aminopyridine, [18F]3F4AP, is a radiofluorinated analog of the FDA-approved drug for multiple sclerosis 4-aminopyridine (4AP). This compound is currently under investigation as a PET tracer for demyelination. We recently described a novel chemical reaction to produce metafluorinated pyridines consisting of direct fluorination of a pyridine N-oxide and the utilization of this reaction for the radiochemical synthesis of [18F]3F4AP. In this article, we demonstrate how to produce this tracer using an automated synthesizer and an in-house made flow hydrogenation reactor. We also show the standard quality control procedures performed before releasing the radiotracer for preclinical animal imaging studies. This semi-automated procedure may serve as the basis for future production of [18F]3F4AP for clinical studies.

Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases

We demonstrate the semi-automated radiochemical synthesis of [18F]3F4AP and quality control procedures.

3-[18F]fluoro-4-aminopyridine, [18F]3F4AP, is a radiofluorinated analog of the FDA-approved drug for multiple sclerosis 4-aminopyridine (4AP). This ...

'Boden Food Plate': Novel Interactive Web-based Method for the Assessment of Dietary Intake

Different methods can be used in research to assess dietary intake, many of which are still paper-based. Written estimated food diaries are often utilized in clinical trials, despite being a burden for both study participants and researchers. This method requires participant literacy, it is time consuming, labor intensive, and can easily lead to under-reporting. With advancements in technology, there is a growing interest in electronic diaries that automate the dietary assessment process. These are focused on improving accuracy, reducing both time and cost and providing users with a visual and more enjoyable experience. The methodology presented here aimed to validate the &#39;Boden Food Plate&#39;, a novel web-based platform for self-recording of food and drink items, compared to a traditional estimated food diary. The application was also rated on a satisfaction scale by study participants using a paper-based questionnaire. Sixty-seven participants completed the dietary measures on both the three-day electronic and paper food diaries. For the analysis, only dietary data completed at both study time points (baseline and week six) was utilized. Despite small mean differences between dietary data collection methods, Bland Altman analysis showed fairly wide 95% limits of agreement between the electronic platform and the written estimated food diary and there were few cases which did not fall within the 95% confidence intervals. Overall, participants found the electronic food diary to be more fun than the paper method and as easy to use as hard copy diaries. The new platform has potential as a self-recording tool for the collection of dietary data, particularly when utilized in clinical trial settings. However, further validation studies are needed to improve the validity of this novel electronic dietary data collection tool.

&#039;Boden Food Plate&#039;: Novel Interactive Web-based Method for the Assessment of Dietary Intake

The &#39;Boden Food Plate&#39; is an electronic food diary designed to be an interactive and fun method to collect dietary intake using visual depictions. The purpose of this study was to validate the web-based application against a traditional three-day estimated food diary method.

Different methods can be used in research to assess dietary intake, many of which are still paper-based. Written estimated food diaries are often utilized ...