We thank the dialysis staffs and members of the department of nephrology in Saitama medical center of Jichi Medical University. We would like to thank Editage (www.editage.com) for English language editing.

All participants provided written informed consent. The study was approved by the Institutional Review Board of the Saitama Medical Center, Jichi Medical University, Japan (RIN 15&#8211;104).
1. Device for the monitoring of rSO2
<ol>
	<li>Prepare a NIRS device for measuring tissue oxygenation. This device has four channels and can perform measurement in up to four organs at the same time.</li>
	<li>Prepare a measurement sensor for NIRS monitoring, to evaluate rSO2 values in each organ via transmitting near-infrared light at two wavelengths of attachment.</li>
</ol>
2. Attaching the measurement sensor
<ol>
	<li>Allow each patient to rest in a supine position for at least 5 minutes before HD.</li>
	<li>Attach measurement sensors to the forehead, the right hypochondrium and lower legs to evaluate rSO2 in the brain, liver and lower leg muscles, respectively.</li>
	<li>Monitoring of cerebral oxygenation
	<ol>
		<li>Attach measurement sensors to the forehead of the dominant hemisphere.</li>
	</ol>
	</li>
	<li>Monitoring of hepatic oxygenation
	<ol>
		<li>Prepare echography to measure the depth to the patients&#8217; liver from the body surface. Confirm that this measurement is within 20&#8211;30 mm from the body surface. Next, attach the measurement sensors to the right hypochondrium. 
		NOTE: In this device, rSO2 values should be obtained in deep tissue 20&#8211;30 mm from the body surface. In some instances, the liver may be located in more than 30 mm from the body surface due to the presence of thick subcutaneous fat.</li>
	</ol>
	</li>
	<li>Monitoring of muscle oxygenation
	<ol>
		<li>Attach measurement sensors to the right or bilateral lower legs.</li>
	</ol>
	</li>
	<li>Sensor connection and powering the device
	<ol>
		<li>Connect each sensor to the leads from the device. Next, turn on the device, and start measuring oxygenation.</li>
	</ol>
	</li>
</ol>
3. Puncturing the dialysis shunt and starting monitoring
<ol>
	<li>Puncturing the dialysis shunt
	<ol>
		<li>Puncture the patients&#8217; dialysis shunt to start HD therapy. At this time, measure BP using a digital blood pressure monitor equipped with the dialysis machine and collect blood samples using syringes.</li>
	</ol>
	</li>
	<li>Start monitoring
	<ol>
		<li>After starting HD therapy, start monitoring the tissue oxygenation of the three organs: the brain, liver and lower leg muscle.</li>
	</ol>
	</li>
	<li>Monitoring of rSO2 during HD
	<ol>
		<li>Observe changes in rSO2 values of each organ and measure BP regularly in addition to the usual monitoring performed during HD therapy including heart rate, venous pressure and blood volume. Confirm the attachment area and connection between the sensors and leads.</li>
	</ol>
	</li>
</ol>

<ol>
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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=A+novel+multimodal+computational+system+using+near-infrared+spectroscopy+predicts+the+need+for+ECMO+initiation+in+neonates+with+congenital+diaphragmatic+hernia.">A novel multimodal computational system using near-infrared spectroscopy predicts the need for ECMO initiation in neonates with congenital diaphragmatic hernia.</a> Journal of Pediatric Surgery. 53 (1), 152-158 (2018).</li><li>MacEwen, C., Sutherland, S., Daly, J., Pugh, C., Tarassenko, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relationship+between+Hypotension+and+Cerebral+Ischemia+during+Hemodialysis.">Relationship between Hypotension and Cerebral Ischemia during Hemodialysis.</a> Journal of the American Socociety of Nephrology. 28 (8), 2511-2520 (2017).</li><li>Polinder-Bos, H. 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=Changes+in+cerebral+oxygenation+and+cerebral+blood+flow+during+hemodialysis+-+A+simultaneous+near-infrared+spectroscopy+and+positron+emission+tomography+study.">Changes in cerebral oxygenation and cerebral blood flow during hemodialysis - A simultaneous near-infrared spectroscopy and positron emission tomography study.</a> Journal of Cerebral Blood Flow &amp; Metablism. 40 (2), 328-340 (2020).</li><li>Ookawara, S., 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=Differences+in+tissue+oxygenation+and+changes+in+total+hemoglobin+signal+strength+in+the+brain,+liver,+and+lower-limb+muscle+during+hemodialysis.">Differences in tissue oxygenation and changes in total hemoglobin signal strength in the brain, liver, and lower-limb muscle during hemodialysis.</a> Journal of Artificial Organs. 21 (1), 86-93 (2018).</li><li>Malik, J., 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+ischemia+worsens+during+hemodialysis+in+end-stage+renal+disease+patients.">Tissue ischemia worsens during hemodialysis in end-stage renal disease patients.</a> The Journal of Vascular Access. 18 (1), 47-51 (2017).</li><li>Ito, K., 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=Cerebral+oxygenation+improvement+is+associated+with+hemoglobin+increase+after+hemodialysis+initiation.">Cerebral oxygenation improvement is associated with hemoglobin increase after hemodialysis initiation.</a> TheInternational Journal of Artificial Organs. , (2020).</li><li>Valerianova, 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=Factors+responsible+for+cerebral+hypoxia+in+hemodialysis+population.">Factors responsible for cerebral hypoxia in hemodialysis population.</a> Physiological Research. 68 (4), 651-658 (2019).</li><li>Ookawara, S., 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=Associations+of+cerebral+oxygenation+with+hemoglobin+levels+evaluated+by+near-infrared+spectroscopy+in+hemodialysis+patients.">Associations of cerebral oxygenation with hemoglobin levels evaluated by near-infrared spectroscopy in hemodialysis patients.</a> PLoS One. 15 (8), 0236720 (2020).</li><li>Kovarova, L., 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=Low+Cerebral+Oxygenation+Is+Associated+with+Cognitive+Impairment+in+Chronic+Hemodialysis+Patients.">Low Cerebral Oxygenation Is Associated with Cognitive Impairment in Chronic Hemodialysis Patients.</a> Nephron. 139 (2), 113-119 (2018).</li><li>Miyazawa, H., 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=Association+of+cerebral+oxygenation+with+estimated+glomerular+filtration+rate+and+cognitive+function+in+chronic+kidney+disease+patients+without+dialysis+therapy.">Association of cerebral oxygenation with estimated glomerular filtration rate and cognitive function in chronic kidney disease patients without dialysis therapy.</a> PLoS One. 13 (6), 0199366 (2018).</li><li>Locatelli, F., 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=Haemodialysis+with+on-line+monitoring+equipment:+tools+or+toys.">Haemodialysis with on-line monitoring equipment: tools or toys.</a> Nephrology Dialysis Transplantation. 20 (1), 22-33 (2005).</li><li>Cordtz, J., Olde, B., Solem, K., Ladefoged, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+venous+oxygen+saturation+and+thoracic+admittance+during+dialysis:+new+approaches+to+hemodynamic+monitoring.">Central venous oxygen saturation and thoracic admittance during dialysis: new approaches to hemodynamic monitoring.</a> Hemodialysis International. 12 (3), 369-377 (2008).</li><li>Kamijo, Y., 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=Continuous+monitoring+of+blood+pressure+by+analyzing+the+blood+flow+sound+of+arteriovenous+fistula+in+hemodialysis+patients.">Continuous monitoring of blood pressure by analyzing the blood flow sound of arteriovenous fistula in hemodialysis patients.</a> Clinical and Experimental Nephrology. 22 (3), 677-683 (2018).</li><li>Ito, K., 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=Factors+affecting+cerebral+oxygenation+in+hemodialysis+patients:+cerebral+oxygenation+associates+with+pH,+hemodialysis+duration,+serum+albumin+concentration,+and+diabetes+mellitus.">Factors affecting cerebral oxygenation in hemodialysis patients: cerebral oxygenation associates with pH, hemodialysis duration, serum albumin concentration, and diabetes mellitus.</a> PLoS One. 10 (2), 0117474 (2015).</li><li>Imai, S., 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=Deterioration+of+Hepatic+Oxygenation+Precedes+an+Onset+of+Intradialytic+Hypotension+with+Little+Change+in+Blood+Volume+during+Hemodialysis.">Deterioration of Hepatic Oxygenation Precedes an Onset of Intradialytic Hypotension with Little Change in Blood Volume during Hemodialysis.</a> Blood Purification. 45 (4), 345-346 (2018).</li><li>Cho, A. R., Kwon, J. Y., Kim, C., Hong, J. M., Kang, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+sensor+location+on+regional+cerebral+oxygen+saturation+measured+by+INVOS+5100+in+on-pump+cardiac+surgery.">Effect of sensor location on regional cerebral oxygen saturation measured by INVOS 5100 in on-pump cardiac surgery.</a> Journal of Anesthesia. 31 (2), 178-184 (2017).</li><li>Ito, K., 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=Deterioration+of+cerebral+oxygenation+by+aortic+arch+calcification+progression+in+patients+undergoing+hemodialysis:+A+cross-sectional+study.">Deterioration of cerebral oxygenation by aortic arch calcification progression in patients undergoing hemodialysis: A cross-sectional study.</a> BioMed Research International. , 2852514 (2017).</li><li>Ito, K., 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=Blood+transfusion+during+haemodialysis+improves+systemic+tissue+oxygenation:+A+case+report.">Blood transfusion during haemodialysis improves systemic tissue oxygenation: A case report.</a> Nefrologia. 37 (4), 435-437 (2017).</li><li>Ito, K., 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=Improvement+of+bilateral+lower-limb+muscle+oxygenation+by+low-density+lipoprotein+apheresis+in+a+patient+with+peripheral+artery+disease+undergoing+hemodialysis.">Improvement of bilateral lower-limb muscle oxygenation by low-density lipoprotein apheresis in a patient with peripheral artery disease undergoing hemodialysis.</a> Nefrologia. 39 (1), 90-92 (2019).</li><li>Kitano, T., 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=Changes+in+tissue+oxygenation+in+response+to+sudden+intradialytic+hypotension.">Changes in tissue oxygenation in response to sudden intradialytic hypotension.</a> Journal of Artificial Organs. 23 (2), 187-190 (2020).</li><li>Lemmers, P. M. A., Toet, M. C., van Bel, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+patent+ductus+arteriosus+and+subsequent+therapy+with+indomethacin+on+cerebral+oxygenation+in+preterm+infants.">Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants.</a> Pediatrics. 121, 142-147 (2008).</li><li>Ito, K., 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=Sleep+apnea+syndrome+caused+lowering+of+cerebral+oxygenation+in+a+hemodialysis+patient:+a+case+report+and+literature+review.">Sleep apnea syndrome caused lowering of cerebral oxygenation in a hemodialysis patient: a case report and literature review.</a> Renal Replacement Therapy. 4, 54 (2018).</li><li>Minato, S., 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=Continuous+monitoring+of+changes+in+cerebral+oxygenation+during+hemodialysis+in+a+patient+with+acute+congestive+heart+failure.">Continuous monitoring of changes in cerebral oxygenation during hemodialysis in a patient with acute congestive heart failure.</a> Journal of Artificial Organs. , (2019).</li></ol>

No conflicts of interest.

NIRS monitoring has been mainly used to evaluate cerebral rSO2, especially in cardiovascular or cerebrovascular surgeries, which require extracorporeal circulation. During extracorporeal circulation including HD therapy, some organs could show relative ischemia7,17,18; however, it remains unclear whether tissue oxygenation becomes low or not. Muscle cramps or abdominal pain during HD could be one of the prodromal symp...

Near-infrared spectroscopy (NIRS) has been used to evaluate regional oxygen saturation (rSO2), a marker of tissue oxygenation, especially cerebral oxygenation in various clinical settings1,2,3 and has recently been applied to patients undergoing hemodialysis (HD)4,5,6,7,8,9,10,11. Cerebral rSO2 is reportedly associated with cognitive function in patients undergoing HD or those with non-dialyzed chronic kidney disease (CKD)11,12. However, thus far, the use of NIRS monitoring has been limited in patients with CKD.
As NIRS monitoring is real-time and noninvasive, we assessed its usefulness as a monitoring device in patients undergoing HD. Although NIRS is mainly used to measure cerebral rSO2, we also investigated rSO2 values in other organs during HD. Specifically, the rSO2 measurement sensors were attached to the forehead, the right hypochondrium and the lower legs to evaluate rSO2 in the brain, liver and lower muscles, respectively. The results showed that NIRS monitoring could be a new approach to clarify changes in organ oxygenation during HD or factors affecting tissue oxygenation in CKD patients.
To date, continuous monitoring was performed during HD, blood volume monitoring, central venous oxygen saturation, thoracic admittance and electronic stethoscope-guided estimated blood pressure (BP) in clinical settings13,14,15; however, there are limitations for the prediction of hypotension or the wide use of devices. In contrast, the new noninvasive approach here could provide real-time information on intradialytic oxygen dynamics in individual organs. Therefore, this monitoring method may allow the detection of transient organ ischemia in the early phases of intradialytic hypotension and may also permit the safe performance of HD. This article describes a protocol to measure tissue oxygenation represented by rSO2, as applied in patients undergoing HD.

<table>
	<tbody>
		<tr>
			<td>DBB-100NX</td>
			<td>Nikkiso</td>
			<td>DBB-100NX</td>
			<td>Dialysis machine</td>
		</tr>
		<tr>
			<td>INVOS 5100c</td>
			<td>Covidien Japan</td>
			<td>INVOSTM 5100c</td>
			<td>tissue oxygenation device</td>
		</tr>
		<tr>
			<td>SOMASENSER</td>
			<td>Covidien Japan</td>
			<td>CV-SAFB-SM/INTL</td>
			<td>NIRS sensor</td>
		</tr>
	</tbody>
</table>

measurement of tissue oxygenation using near-infrared spectroscopy in patients undergoing hemodialysis

Near-infrared spectroscopy (NIRS) has recently been applied as a tool to measure regional oxygen saturation (rSO2), a marker of tissue oxygenation, in clinical settings including cardiovascular and brain surgery, neonatal monitoring and prehospital medicine. The NIRS monitoring devices are real-time and noninvasive, and have mainly been used for evaluating cerebral oxygenation in critically ill patients during an operation or intensive care. Thus far, the use of NIRS monitoring in patients with chronic kidney disease (CKD) including hemodialysis (HD) has been limited; therefore, we investigated rSO2 values in some organs during HD. We monitored rSO2 values using a NIRS device transmitting near-infrared light at 2 wavelengths of attachment. The HD patients were placed in a supine position, with rSO2 measurement sensors attached to the foreheads, the right hypochondrium and the lower legs to evaluate rSO2 in the brain, liver and lower leg muscles, respectively. NIRS monitoring could be a new approach to clarify changes in organ oxygenation during HD or factors affecting tissue oxygenation in CKD patients. This article describes a protocol to measure tissue oxygenation represented by rSO2 as applied in HD patients.

Cerebral rSO2 values before HD were lower than those in healthy subjects and cerebral rSO2 in HD patients with diabetes mellitus (DM) were lower than those in HD patients without DM (Figure 1)16. Furthermore, although tissue oxygenation continues without a decrease of BP during HD, we incidentally observed changes in cerebral and hepatic rSO2 due to intradialytic hypotension (Figure 2). Due to the continuo...

Watch this Scientific Journal Video about Measurement of Tissue Oxygenation Using Near-Infrared Spectroscopy in Patients Undergoing Hemodialysis at JoVE.com

Measurement of Tissue Oxygenation Using Near-Infrared Spectroscopy in Patients Undergoing Hemodialysis

We present a protocol to measure regional oxygen saturation (rSO2) in hemodialysis (HD) patients by using a near-infrared spectroscopy monitor. The rSO2 value is an index of tissue oxygenation. This noninvasive and real-time monitoring could be useful for confirming changes in organ oxygenation during HD.

Near-infrared spectroscopy (NIRS) has recently been applied as a tool to measure regional oxygen saturation (rSO2), a marker of tissue oxygenation, in ...

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2.0K Views.  Jichi Medical University. We present a protocol to measure regional oxygen saturation (rSO2) in hemodialysis (HD) patients by using a near-infrared spectroscopy monitor. The rSO2 value is an index of tissue oxygenation. This noninvasive and real-time monitoring could be useful for confirming changes in organ oxygenation during HD.

Video: Measurement of Tissue Oxygenation Using Near-Infrared Spectroscopy in Patients Undergoing Hemodialysis

Dual-mode Imaging of Cutaneous Tissue Oxygenation and Vascular Function

Accurate assessment of cutaneous tissue oxygenation and vascular function is important for appropriate detection, staging, and treatment of many health disorders such as chronic wounds. We report the development of a dual-mode imaging system for non-invasive and non-contact imaging of cutaneous tissue oxygenation and vascular function. The imaging system integrated an infrared camera, a CCD camera, a liquid crystal tunable filter and a high intensity fiber light source. A Labview interface was programmed for equipment control, synchronization, image acquisition, processing, and visualization. Multispectral images captured by the CCD camera were used to reconstruct the tissue oxygenation map. Dynamic thermographic images captured by the infrared camera were used to reconstruct the vascular function map. Cutaneous tissue oxygenation and vascular function images were co-registered through fiduciary markers. The performance characteristics of the dual-mode image system were tested in humans.

A dual-mode imaging system was developed for non-contact assessment of cutaneous tissue oxygenation and vascular function.

Accurate assessment of cutaneous tissue oxygenation and vascular function is important for appropriate detection, staging, and treatment of many health ...

Near Infrared Optical Projection Tomography for Assessments of &beta;-cell Mass Distribution in Diabetes Research

By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR)2; 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction2 and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations3. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans.

Near Infrared Optical Projection Tomography for Assessments of &amp;#946;-cell Mass Distribution in Diabetes Research

We describe the adaptation of optical projection tomography (OPT)1 to imaging in the near infrared spectrum, and the implementation of a number of computational tools. These protocols enable assessments of pancreatic &beta;-cell mass (BCM) in larger specimens, increase the multichannel capacity of the technique and increase the quality of OPT data.

By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of ...

Tissue-simulating Phantoms for Assessing Potential Near-infrared Fluorescence Imaging Applications in Breast Cancer Surgery

Inaccuracies in intraoperative tumor localization and evaluation of surgical margin status result in suboptimal outcome of breast-conserving surgery (BCS). Optical imaging, in particular near-infrared fluorescence (NIRF) imaging, might reduce the frequency of positive surgical margins following BCS by providing the surgeon with a tool for pre- and intraoperative tumor localization in real-time. In the current study, the potential of NIRF-guided BCS is evaluated using tissue-simulating breast phantoms for reasons of standardization and training purposes.
Breast phantoms with optical characteristics comparable to those of normal breast tissue were used to simulate breast conserving surgery. Tumor-simulating inclusions containing the fluorescent dye indocyanine green (ICG) were incorporated in the phantoms at predefined locations and imaged for pre- and intraoperative tumor localization, real-time NIRF-guided tumor resection, NIRF-guided evaluation on the extent of surgery, and postoperative assessment of surgical margins. A customized NIRF camera was used as a clinical prototype for imaging purposes.
Breast phantoms containing tumor-simulating inclusions offer a simple, inexpensive, and versatile tool to simulate and evaluate intraoperative tumor imaging. The gelatinous phantoms have elastic properties similar to human tissue and can be cut using conventional surgical instruments. Moreover, the phantoms contain hemoglobin and intralipid for mimicking absorption and scattering of photons, respectively, creating uniform optical properties similar to human breast tissue. The main drawback of NIRF imaging is the limited penetration depth of photons when propagating through tissue, which hinders (noninvasive) imaging of deep-seated tumors with epi-illumination strategies.

Near-infrared fluorescence (NIRF) imaging may improve therapeutic outcome of breast cancer surgery by enabling intraoperative tumor localization and evaluation of surgical margin status. Using tissue-simulating breast phantoms containing fluorescent tumor-simulating inclusions, potential clinical applications of NIRF imaging in breast cancer patients can be assessed for standardization and training purposes.

Inaccuracies in intraoperative tumor localization and evaluation of surgical margin status result in suboptimal outcome of breast-conserving surgery ...

Combined Near-infrared Fluorescent Imaging and Micro-computed Tomography for Directly Visualizing Cerebral Thromboemboli

Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of stroke than relying on indirect measurements, and will be a potent and robust vascular research tool. We use an optical imaging approach that labels thrombi with a molecular imaging thrombus marker&#160;&#8212; a Cy5.5 near-infrared fluorescent (NIRF) probe that is covalently linked to the fibrin strands of the thrombus by the fibrin-crosslinking enzymatic action of activated coagulation factor XIIIa during the process of clot maturation. A micro-computed tomography (microCT)-based approach uses thrombus-seeking gold nanoparticles (AuNPs) functionalized to target the major component of the clot: fibrin. This paper describes a detailed protocol for the combined in vivo microCT and ex vivo NIRF imaging of thromboemboli in a mouse model of embolic stroke. We show that in vivo microCT and fibrin-targeted glycol-chitosan AuNPs (fib-GC-AuNPs) can be used for visualizing both in situ thrombi and cerebral embolic thrombi. We also describe the use of in vivo microCT-based direct thrombus imaging to serially monitor the therapeutic effects of tissue plasminogen activator-mediated thrombolysis. After the last imaging session, we demonstrate by ex vivo NIRF imaging the extent and the distribution of residual thromboemboli in the brain. Finally, we describe quantitative image analyses of microCT and NIRF imaging data. The combined technique of direct thrombus imaging allows two independent methods of thrombus visualization to be compared: the area of thrombus-related fluorescent signal on ex vivo NIRF imaging vs. the volume of hyperdense microCT thrombi in vivo.

This protocol describes the application of combined near-infrared fluorescent (NIRF) imaging and micro-computed tomography (microCT) for visualizing cerebral thromboemboli. This technique allows the quantification of thrombus burden and evolution. The NIRF imaging technique visualizes fluorescently labeled thrombus in excised brain, while the microCT technique visualizes thrombus inside living animals using gold-nanoparticles.

Direct thrombus imaging visualizes the root cause of thromboembolic infarction. Being able to image thrombus directly allows far better investigation of ...

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and lower quality of life. Persistent postsurgical pain is relatively refractory to treatment hence generating a high need for preventive strategies and treatments. Therefore, the identification of patients at risk of developing persistent pain is an area of active ongoing research. Recently it was demonstrated that peri-operative disruptions in central pain processing may be able to predict persistent postsurgical pain at long term follow-up in breast cancer patients. The aim of the current report is to present a short protocol to obtain pain thresholds to different stimuli at multiple sites and a measure of endogenous analgesia in breast cancer patients. We have used this method successfully in a clinical context and detail some representative results from a clinical study.

Persistent postsurgical pain may be related to changes in pain processing. By assessing pain in response to standardized stimuli, changes in pain processing can be elucidated. We present methods to obtain pain thresholds to different stimuli and a measure of endogenous analgesia in patients undergoing breast cancer surgery.

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and ...

Skeletal Muscle Neurovascular Coupling, Oxidative Capacity, and Microvascular Function with 'One Stop Shop' Near-infrared Spectroscopy

Exercise represents a major hemodynamic stress that demands a highly coordinated neurovascular response in order to match oxygen delivery to metabolic demand. Reactive hyperemia (in response to a brief period of tissue ischemia) is an independent predictor of cardiovascular events and provides important insight into vascular health and vasodilatory capacity. Skeletal muscle oxidative capacity is equally important in health and disease, as it determines the energy supply for myocellular processes. Here, we describe a simple, non-invasive approach using near-infrared spectroscopy to assess each of these major clinical endpoints (reactive hyperemia, neurovascular coupling, and muscle oxidative capacity) during a single clinic or laboratory visit. Unlike Doppler ultrasound, magnetic resonance images/spectroscopy, or invasive catheter-based flow measurements or muscle biopsies, our approach is less operator-dependent, low-cost, and completely non-invasive. Representative data from our lab taken together with summary data from previously published literature illustrate the utility of each of these end-points. Once this technique is mastered, application to clinical populations will provide important mechanistic insight into exercise intolerance and cardiovascular dysfunction.

Skeletal Muscle Neurovascular Coupling, Oxidative Capacity, and Microvascular Function with &#039;One Stop Shop&#039; Near-infrared Spectroscopy

Here, we describe a simple, non-invasive approach using near-infrared spectroscopy to assess reactive hyperemia, neurovascular coupling and skeletal muscle oxidative capacity in a single clinic or laboratory visit.

Exercise represents a major hemodynamic stress that demands a highly coordinated neurovascular response in order to match oxygen delivery to metabolic ...

How to Administer Near-Infrared Spectroscopy in Critically ill Neonates, Infants, and Children

Near infrared spectroscopy (NIRS) calculates regional tissue oxygenation (rSO2) using the different absorption spectra of oxygenated and deoxygenated hemoglobin molecules. A probe placed on the skin emits light that is absorbed, scattered, and reflected by the underlying tissue. Detectors in the probe sense the amount of reflected light: this reflects the organ-specific ratio of oxygen supply and consumption - independent of pulsatile flow. Modern devices enable the simultaneous monitoring at different body sites. A rise or dip in the rSO2 curve visualizes changes in oxygen supply or demand before vital signs indicate them. The evolution of rSO2 values in relation to the starting point is more important for interpretation than are absolute values.
A routine clinical application of NIRS is the surveillance of somatic and cerebral oxygenation during and after cardiac surgery. It is also administered in preterm infants at risk for necrotizing enterocolitis, newborns with hypoxic ischemic encephalopathy and a potential risk of impaired tissue oxygenation. In the future, NIRS could be increasingly used in multimodal neuromonitoring, or applied to monitor patients with other conditions (e.g., after resuscitation or traumatic brain injury).

This protocol is designed to assist clinicians to measure regional tissue oxygenation at different body sites in infants and children. It can be used in situations where tissue oxygenation is potentially compromised, particularly during cardiopulmonary bypass, when using non-pulsatile cardiac-assist devices, and in critically ill neonates, infants and children.

Near infrared spectroscopy (NIRS) calculates regional tissue oxygenation (rSO2) using the different absorption spectra of oxygenated and deoxygenated ...

Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination

The efficacy of photoimmunotherapy can be evaluated more accurately with an orthotopic mouse model than with a subcutaneous one. A pleural dissemination model can be used for the evaluation of treatment methods for intrathoracic diseases such as lung cancer or malignant pleural mesothelioma.
Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment strategy that combines the specificity of tumor-targeting antibodies with toxicity caused by a photoabsorber (IR700Dye) after exposure to NIR light. The efficacy of NIR-PIT has been reported using various antibodies; however, only a few reports have shown the therapeutic effect of this strategy in an orthotopic model. In the present study, we demonstrate an example of efficacy evaluation of the pleural disseminated lung cancer model, which was treated using NIR-PIT.

Near-infrared photoimmunotherapy (NIR-PIT) is an emerging cancer therapeutic strategy that utilizes an antibody-photoabsorber (IR700Dye) conjugate and NIR light to destroy cancer cells. Here, we present a method to evaluate the antitumor effect of NIR-PIT in a mouse model of pleural disseminated lung cancer and malignant pleural mesothelioma using bioluminescence imaging.

The efficacy of photoimmunotherapy can be evaluated more accurately with an orthotopic mouse model than with a subcutaneous one. A pleural dissemination ...

Evaluation of Hydration Status by Bioelectrical Impedance Vector Analysis in Patients with Ischemic Heart Disease Undergoing Exercise Stress Test

Ischemic heart disease (IHD) represents a group of clinical syndromes characterized by myocardial ischemia, leading to an impairment in the myocardial blood supply and compromised perfusion. Several clinical variables assessed through a stress test, such as oxygen uptake (VO2) and heart rate oxygen pulse (HR/O2), have been attributed as cardiopulmonary prognostic factors in patients with IHD. However, other factors like hydration status (HS), potentially affecting the cardiopulmonary response, have been barely addressed. Unbalanced HS has a short-term effect on plasma volume and the sympathetic nervous system, which impacts blood volume, and lowers VO2 and HR/O2. Recently, bioelectrical impedance analysis (BIA), a method based on the opposition of body tissues (including fluid volume) to a low electrical current, has been widely used to assess HS by obtaining two components: resistance (R) and reactance (Xc) and using prediction formulas. However, several limitations as chronic illness or abnormal fluid status, may affect the results. In this sense, alternative BIA methods, such as bioelectrical impedance vector analysis (BIVA), have become relevant. R and Xc (adjusted by height) result in a vector plotted on the R/Xc graph, which allows interpreting the HS as normal or abnormal according to the distance of the mean vector. This study aims to describe how to determine HS by BIVA using a single-frequency device and compare the results with the cardiopulmonary response in patients with IHD.

Hydration status imbalances can have a short-term effect on direct and indirect determinants of oxygen uptake and pulse, and morbidity and mortality prognostic factors in ischemic heart disease. This protocol describes the technique for assessment of hydration status through bioelectrical impedance vector analysis and cardiopulmonary response during exercise stress test.

Ischemic heart disease (IHD) represents a group of clinical syndromes characterized by myocardial ischemia, leading to an impairment in the myocardial ...

Functional OT and Near-IR Spectroscopy to Study Brain Function Remodeling

Investigating the Effect of Different Types of Exercise on Upper Limb Functional Recovery in Patients with Right Hemisphere Damage Based on fNIRS

To investigate the effects of functional occupational therapy (FOT) combined with different types of exercise on upper limb motor function recovery and brain function remodeling in patients with right hemisphere damage (RHD) by analyzing functional near-infrared spectroscopy (fNIRS). Patients (n = 32) with RHD at Beijing Bo'ai Hospital were recruited and randomly allocated to receive either FOT combined with passive motion (N=16) or FOT combined with assisted active movement (N=16). The passive motion group (FOT-PM) received functional occupational therapy for 20 min and passive exercise for 10 min in each session, while the assisted active movement group (FOT-AAM) received functional occupational therapy for 20 min and assisted active exercise for 10 min. Both groups received conventional drug therapy and other rehabilitation therapy. Treatment was performed once a day, 5 times a week for 4 weeks. The recovery of motor function and activities of daily living (ADL) was assessed using Fugl-Meyer Assessment upper extremity (FMA-UE) and modified Barthel index (MBI) before and after treatment, and brain activation of the bilateral motor area was analyzed with fNIRS. The findings suggested that FOT combined with AAM was more effective than FOT combined with PM in improving the motor function of RHD patients' upper limbs and fingers, improving their ability to perform activities of daily living, and facilitating brain function remodeling of the motor area.

Author Spotlight: Advancing Upper Limb Rehabilitation in Patients with Right Hemisphere Damage Using Assisted Active Exercise

Here, we investigate the effect of functional occupational therapy combined with assisted active or passive motion on the upper limb function of patients with right hemisphere damage and explore the effect of functional near-infrared spectroscopy on brain function remodeling.

To investigate the effects of functional occupational therapy (FOT) combined with different types of exercise on upper limb motor function recovery and ...