scholarly journals The Cole Relaxation Frequency as a Parameter to Identify Cancer in Lung Tissue: Preliminary Animal and ex vivo Patient Studies

2021 ◽  
Author(s):  
Les Bogdanowicz ◽  
Onur Fidaner ◽  
Donato Ceres ◽  
Alex Grycuk ◽  
Davis Demos
Keyword(s):  
Lung Cancer ◽  
Ex Vivo ◽  
Human Subjects ◽  
Small Animal ◽  
Relaxation Frequency ◽  
Normal Tissues ◽  
Electrical Bioimpedance ◽  
Benign Nodules ◽  
Porcine Lungs

Abstract Lung cancer is the world’s leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules. The Cole Relaxation Frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues. Here we show that CRF allows for diagnosis of cancer in human subjects, based on evaluation of 60 specimens obtained from 30 patients. We observed clear discrimination of CRF values in tumor and distant normal tissues, resulting in a high degree of sensitivity (97%) and specificity (87%) in cancer diagnosis. Furthermore, we tested 20 xenograft small animal model specimens, observing a similar separation of CRF values as in the human in-vivo measurements. We also obtained CRF measurements in pressurized and unpressurized lungs by implanting tumors into ex-vivo porcine lungs. CRF measurements align with previous tests in human and small animal models.

The Cole Relaxation Frequency as a Parameter to Identify Cancer in Lung Tissue: Preliminary Animal and ex vivo Patient Studies (Preprint)

2021 ◽  
Author(s):  
Les Bogdanowicz ◽  
Onur Fidaner ◽  
Donato Ceres ◽  
Alex Grycuk ◽  
David Demos
Keyword(s):  
Lung Cancer ◽  
Ex Vivo ◽  
Human Subjects ◽  
Small Animal ◽  
Relaxation Frequency ◽  
Normal Tissues ◽  
Electrical Bioimpedance ◽  
Benign Nodules ◽  
Porcine Lungs

UNSTRUCTURED Lung cancer is the world’s leading cause of cancer deaths, and diagnosis remains challenging. Lung cancer starts as small nodules; early and accurate diagnosis allows timely surgical resection of malignant nodules while avoiding unnecessary surgery in patients with benign nodules. The Cole Relaxation Frequency (CRF) is a derived electrical bioimpedance signature, which may be utilized to distinguish cancerous tissues from normal tissues. Here we show that CRF allows for diagnosis of cancer in human subjects, based on evaluation of 60 specimens obtained from 30 patients. We observed clear discrimination of CRF values in tumor and distant normal tissues, resulting in a high degree of sensitivity (97%) and specificity (87%) in cancer diagnosis. Furthermore, we tested 20 xenograft small animal model specimens, observing a similar separation of CRF values as in the human in-vivo measurements. We also obtained CRF measurements in pressurized and unpressurized lungs by implanting tumors into ex-vivo porcine lungs. CRF measurements align with previous tests in human and small animal models.

scholarly journals MITOCHONDRIAL REDOX IMAGING FOR CANCER DIAGNOSTIC AND THERAPEUTIC STUDIES

2009 ◽  
Vol 02 (04) ◽  
pp. 325-341 ◽  
Author(s):  
LIN Z. LI ◽  
HE N. XU ◽  
MAHSA RANJI ◽  
SHOKO NIOKA ◽  
BRITTON CHANCE
Keyword(s):  
Ex Vivo ◽  
Small Animal ◽  
Redox Status ◽  
Metabolic Imaging ◽  
Scanning Method ◽  
Normal Tissues ◽  
Cancer Diagnostic ◽  
Technical Developments ◽  
Imaging Results

Mitochondrial redox states provide important information about energy-linked biological processes and signaling events in tissues for various disease phenotypes including cancer. The redox scanning method developed at the Chance laboratory about 30 years ago has allowed 3D high-resolution (~50 × 50 × 10 μm3) imaging of mitochondrial redox state in tissue on the basis of the fluorescence of NADH (reduced nicotinamide adenine dinucleotide) and Fp (oxidized flavoproteins including flavin adenine dinucleotide, i.e., FAD). In this review, we illustrate its basic principles, recent technical developments, and biomedical applications to cancer diagnostic and therapeutic studies in small animal models. Recently developed calibration procedures for the redox imaging using reference standards allow quantification of nominal NADH and Fp concentrations, and the concentration-based redox ratios, e.g., Fp/(Fp+NADH) and NADH/(Fp+NADH) in tissues. This calibration facilitates the comparison of redox imaging results acquired for different metabolic states at different times and/or with different instrumental settings. A redox imager using a CCD detector has been developed to acquire 3D images faster and with a higher in-plane resolution down to 10 μm. Ex vivo imaging and in vivo imaging of tissue mitochondrial redox status have been demonstrated with the CCD imager. Applications of tissue redox imaging in small animal cancer models include metabolic imaging of glioma and myc-induced mouse mammary tumors, predicting the metastatic potentials of human melanoma and breast cancer mouse xenografts, differentiating precancerous and normal tissues, and monitoring the tumor treatment response to photodynamic therapy. Possible future directions for the development of redox imaging are also discussed.

scholarly journals In VivoVisualization of Heterogeneous Intratumoral Distribution of Hypoxia-Inducible Factor-1αActivity by the Fusion of High-Resolution SPECT and Morphological Imaging Tests

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Hirofumi Fujii ◽  
Masayuki Yamaguchi ◽  
Kazumasa Inoue ◽  
Yasuko Mutou ◽  
Masashi Ueda ◽  
...  
Keyword(s):  
High Resolution ◽  
Ex Vivo ◽  
Hypoxia Inducible Factor ◽  
Chimeric Protein ◽  
Small Animal ◽  
Ct Scanner ◽  
Heterogeneous Distribution ◽  
Fusion Images ◽  
Intratumoral Distribution

Purpose. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α(HIF) activity in tumor tissuesin vivo.Methods. We synthesized of125I-IPOS, a125I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of125I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of125I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtainedin vivoSPECT-CT fusion images were compared withex vivoimages of excised tumors. Fusion imaging with MRI was also examined.Results.125I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of125I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of125I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of125I-IPOS.Conclusion. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of125I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activityin vivo.

scholarly journals In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte
Keyword(s):  
In Vivo Imaging ◽  
Ex Vivo ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Benzodiazepine Receptors ◽  
Small Animal ◽  
Small Animal Pet ◽  
Planar Imaging ◽  
Peripheral Benzodiazepine Receptors

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

scholarly journals Design of a drop-in EBI sensor probe for abnormal tissue detection in minimally invasive surgery

2020 ◽  
Vol 11 (1) ◽  
pp. 87-95
Author(s):  
Guanming Zhu ◽  
Liang Zhou ◽  
Shilong Wang ◽  
Pengjie Lin ◽  
Jing Guo ◽  
...  
Keyword(s):  
Minimally Invasive Surgery ◽  
Minimally Invasive ◽  
Invasive Surgery ◽  
Resection Margin ◽  
Ex Vivo ◽  
Porcine Liver ◽  
Normal Tissues ◽  
Electrical Bioimpedance ◽  
Sensor Probe ◽  
Abnormal Tissue

AbstractIt is a common challenge for the surgeon to detect pathological tissues and determine the resection margin during a minimally invasive surgery. In this study, we present a drop-in sensor probe based on the electrical bioimpedance spectroscopic technology, which can be grasped by a laparoscopic forceps and controlled by the surgeon to inspect suspicious tissue area conveniently. The probe is designed with an optimized electrode and a suitable shape specifically for Minimally Invasive Surgery (MIS). Subsequently, a series of ex vivo experiments are carried out with porcine liver tissue for feasibility validation. During the experiments, impedance measured at frequencies from 1 kHz to 2 MHz are collected on both normal tissues and water soaked tissue. In addition, classifiers based on discriminant analysis are developed. The result of the experiment indicate that the sensor probe can be used to measure the impedance of the tissue easily and the developed tissue classifier achieved accuracy of 80% and 100% respectively.

Abstract 1767: Feasibility of In Vivo Cardiac Stem Cell Tracking, by SPECT and PET Imaging, Using the Sodium-iodide Symporter as Reporter Gene

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
John Terrovitis ◽  
Keng Fai Kwok ◽  
Riikka Läutamaki ◽  
James M Engles ◽  
Andreas S Barth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Reporter Gene ◽  
Cell Tracking ◽  
Ex Vivo ◽  
Small Animal ◽  
Cell Labeling ◽  
Sodium Iodide Symporter ◽  
Cell Injection

Background. Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo . Aim. To develop a reporter gene that permits in vivo stem cell labeling. We examined the sodium-iodide symporter (NIS), a protein that is not expressed in the heart, but promotes cellular uptake of 99m Tc or 124 I, thus permitting cell tracking by SPECT or PET imaging, respectively. Methods. The human NIS gene ( h NIS) was expressed in rat cardiac derived stem cells (rCDCs) using lentivirus driven by the CAG or CMV promoter. NIS function in transduced cells was confirmed by in vitro 99m Tc uptake. Eleven rats were injected with 1 or 2 million rCDCs intramyocardially immediately after LAD ligation; 6 with CMV-NIS and 5 with CAG-NIS cells. Dual isotope SPECT imaging was performed on a small animal SPECT/CT system, using 99m Tc for cell detection and 201 Tl for myocardial delineation, 24 hrs after cell injection. PET was performed on a small animal PET scanner using 124 I for cell tracking and 13 NH 3 for myocardial delineation, 48hrs after cell injection. Contrast Ratio (CR) was defined as [(signal in the cells)-(signal in blood pool)]/signal in blood pool. High resolution ex vivo SPECT scans of explanted hearts (n=3) were obtained to confirm that in vivo signal was derived from the cell injection site. The presence of h NIS mRNA was confirmed in injected hearts after animal sacrifice (n=2), by real-time RT-PCR. Results. NIS expression in rCDCs did not affect cell viability/proliferation (p=0.718, ctr vs NIS). In vitro 99m Tc uptake was 6.0±0.9% vs 0.07±0.05, without and with perchlorate (specific NIS blocker), respectively. NIS-transduced rCDCs were easily visualized as spots of 99m Tc or 124 I uptake within a perfusion deficit in the SPECT and PET images. CR was considerably higher when cells were transduced by the CMV-NIS virus in comparison to the CAG-NIS virus (70±40% vs 28±29%, p=0.085). Ex vivo small animal SPECT imaging confirmed that in vivo 99m Tc signals were localized to the injection sites. PCR confirmed the presence of h NIS mRNA in injected hearts. Conclusion. NIS expression allows non invasive in vivo stem cell tracking in the myocardium, using both SPECT and PET. This reporter gene has great potential for translation in future clinical applications.

Abstract 401: Experimental Aneurysm in Rats Excluded by Stent Graft: A New Model to Assess the Impact of Endovascular Aneurysm Repair on the Pathophysiology of Abdominal Aortic Aneurysm.

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Martin Rouer ◽  
Martin Rouer ◽  
Jean-Marc Alsac ◽  
Jean-Baptiste Michel
Keyword(s):  
Experimental Model ◽  
Ex Vivo ◽  
Endovascular Aneurysm Repair ◽  
Small Animal ◽  
Normal Diet ◽  
Biological Study ◽  
Experimental Aneurysm ◽  
Midline Laparotomy ◽  
The Impact

Introduction Biological study of the impact of endovascular aortic repair (EVAR) on pathophysiology of aortic abdominal aneurysms (AAA) can only be performed indirectly in humans, by imaging or search for peripheral biomarkers in the circulating blood. Therefore biological mechanism’s modifications into the aneurismal wall related to its endovascular exclusion are still to be elucidated, and small animal models should bring a valuable help in this field. We describe a new experimental model of stentgraft implantation for the exclusion of AAA in rats. Methods Aneurysms were induced as previously described by intra-aortic elastase injection in Wistar rats, or by aortic decellularized xenograft transplantation in Lewis rats. At least 15 days later, the midline laparotomy was reopened, and 3mm covered stentgraft were inserted and deployed in the AAA to obtain its exclusion. The patency of the graft and the AAA exclusion could be assessed by a global arteriogram through the carotid artery. After closure of the laparotomy, the rats were awakened and returned to a normal diet. Results This experimental model of AAA exclusion by a stentgraft allows many in vivo and ex vivo studies of the pathophysiology of AAA after EVAR. Histological modifications of the aortic wall and the intra-luminal thrombus could be assessed. The impact of EVAR on the adventitial immuno-inflammatory activity could be studied by different imaging such as MRI, scintigraphy or PET-scan. In situ biological and enzymatic activities could be evaluated to better understand the local mechanisms leading to AAA shrinkage or expansion after EVAR. Conclusion Exclusion by stentgraft of experimental AAA in rats is the first described model of EVAR in small animals. It is feasible and reproducible for both elastase and xenograft experimental AAA models. This model will definitely help to a better analysis and understanding of the impact of stentgrafting on biological mechanisms in the aneurismal wall, that lead to EVAR success with shrinkage of aneurismal sac or EVAR failure with its continuing expansion.

scholarly journals Baicalin suppresses lung cancer growth by targeting PDZ-binding kinase/T-LAK cell-originated protein kinase

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Xin Diao ◽  
Danfen Yang ◽  
Yu Chen ◽  
Wentian Liu
Keyword(s):  
Lung Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Ex Vivo ◽  
Lung Cancer Cells ◽  
Cancer Growth ◽  
Downstream Signaling ◽  
Lak Cell

AbstractBaicalin is the main bioactive component extracted from the traditional Chinese medicine Baical Skullcap Root, and its anti-tumor activity has been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in many cancer cells and stimulates the tumorigenic properties, and so, it is a pivotal target for agent to cure cancers. We reported for the first time that baicalin suppressed PBK/TOPK activities by directly binding with PBK/TOPK in vitro and in vivo. Ex vivo studies showed that baicalin suppressed PBK/TOPK activity in JB6 Cl41 cells and H441 lung cancer cells. Moreover, knockdown of PBK/TOPK in H441 cells decreased their sensitivity to baicalin. In vivo study indicated that injection of baicalin in H441 tumor-bearing mice effectively suppressed cancer growth. The PBK/TOPK downstream signaling molecules Histone H3 and ERK2 in tumor tissues were also decreased after baicalin treatment. Taken together, baicalin can inhibit proliferation of lung cancer cells as a PBK/TOPK inhibitor both in vitro and in vivo.

scholarly journals Single-cell resolution in high-resolution synchrotron X-ray CT imaging with gold nanoparticles

2013 ◽  
Vol 21 (1) ◽  
pp. 242-250 ◽  
Author(s):  
Elisabeth Schültke ◽  
Ralf Menk ◽  
Bernd Pinzer ◽  
Alberto Astolfo ◽  
Marco Stampanoni ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Single Cell ◽  
Brain Tumour ◽  
Ex Vivo ◽  
Small Animal ◽  
C6 Glioma Cells ◽  
X Ray ◽  
Local Tomography ◽  
The Brain

Gold nanoparticles are excellent intracellular markers in X-ray imaging. Having shown previously the suitability of gold nanoparticles to detect small groups of cells with the synchrotron-based computed tomography (CT) technique bothex vivoandin vivo, it is now demonstrated that even single-cell resolution can be obtained in the brain at leastex vivo. Working in a small animal model of malignant brain tumour, the image quality obtained with different imaging modalities was compared. To generate the brain tumour, 1 × 105C6 glioma cells were loaded with gold nanoparticles and implanted in the right cerebral hemisphere of an adult rat. Raw data were acquired with absorption X-ray CT followed by a local tomography technique based on synchrotron X-ray absorption yielding single-cell resolution. The reconstructed synchrotron X-ray images were compared with images obtained by small animal magnetic resonance imaging. The presence of gold nanoparticles in the tumour tissue was verified in histological sections.

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