Abstract

Tumor biopsies are an important aspect of oncology providing a guide for medical treatment and evaluation of disease progression. Highly heterogenous tumors have complex regions of active cancer cells interdigitated with necrotic tissue and healthy noncancerous tissue. The reliable access to tumor tissue pathology is therefore challenging and usually requires multiple needle insertions with accompanying patient discomfort and risk of infection. Oxygen levels provide a means of detecting and evaluating tumor tissue with levels reduced by 2-fold to 22-fold, depending on the type of organ. However, if the biopsy needle is placed in an area of normal tissue, there is always a chance that no diagnostic cells will be acquired for meaningful pathology and molecular analysis. While not the case in all tumors, there are cases where the in vivo oxygen levels differ with tumor cells having a value of pO2 lying between the anoxic necrotic tissue and normoxic normal tissue. The level of oxygen in tumor cells can also vary with time as related to complex biochemical pathways. The efficacy of radiation therapy is also sensitive to oxygen levels in tumors. Lower levels of oxygen present greater resistance to treatment. To address these concerns, a pO2-guided biopsy needle (OGBN) was developed to determine oxygen levels and fluctuations in highly resolved regions of tumors, in order to aide in determining the optimal region for cell sampling help in determining medical treatment options.

References

1.
McKeown
,
S. R.
,
2014
, “
Defining Normoxia, Physoxia and Hypoxia in Tumours—Implications for Treatment Response
,”
Br. J. Radiol.
,
87
(
1035
), p.
20130676
.10.1259/bjr.20130676
2.
Tatum
,
J. L.
,
2006
, “
Hypoxia: Importance in Tumor Biology, Noninvasive Measurement by Imaging, and Value of Its Measurement in the Management of Cancer Therapy
,”
Int. J. Radiat. Biol.
,
82
(
10
), pp.
699
757
.10.1080/09553000601002324
3.
Kim
,
J. G.
,
Zhao
,
D.
,
Song
,
Y.
,
Constantinescu
,
A.
,
Mason
,
R. P.
, and
Liu
,
H.
,
2003
, “
Interplay of Tumor Vascular Oxygenation and Tumor PO2 Observed Using Near-Infrared Spectroscopy, an Oxygen Needle Electrode, and [Sup 19]F MR PO[Sub 2] Mapping
,”
J. Biomed. Opt.
,
8
(
1
), p.
53
.10.1117/1.1527049
4.
Delprat
,
V.
,
Tellier
,
C.
,
Demazy
,
C.
,
Raes
,
M.
,
Feron
,
O.
, and
Michiels
,
C.
,
2020
, “
Cycling Hypoxia Promotes a Pro-Inflammatory Phenotype in Macrophages Via JNK/P65 Signaling Pathway
,”
Sci. Rep.
,
10
(
1
), p.
882
.10.1038/s41598-020-57677-5
5.
Terris
,
D. J.
,
2000
, “
Head and Neck Cancer: The Importance of Oxygen
,”
Laryngoscope
,
110
, pp.
697
707
.10.1097/00005537-200005000-00001
6.
Bertout
,
J. A.
,
Patel
,
S. A.
, and
Simon
,
M. C.
,
2008
, “
The Impact of O2 Availability on Human Cancer
,”
Nat. Rev. Cancer
,
8
(
12
), pp.
967
975
.10.1038/nrc2540
7.
Simon
,
M. C.
,
2010
,
Diverse Effects of Hypoxia on Tumor Progression
,
Springer-Verlag
,
Heidelberg, New York
.
8.
Kaelin
,
W. G.
,
2017
, “
The VHL Tumor Suppressor Gene: Insights InT\to Oxygen SensIng and Cancer
,”
Trans. Am. Clin. Climatol. Assoc.
,
128
, pp.
298
307
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525432/
9.
Chakraborty
,
A. A.
,
Laukka
,
T.
,
Myllykoski
,
M.
,
Ringel
,
A. E.
,
Booker
,
M. A.
,
Tolstorukov
,
M. Y.
,
Meng
,
Y. J.
,
Meier
,
S. R.
,
Jennings
,
R. B.
,
Creech
,
A. L.
,
Herbert
,
Z. T.
,
McBrayer
,
S. K.
,
Olenchock
,
B. A.
,
Jaffe
,
J. D.
,
Haigis
,
M. C.
,
Beroukhim
,
R.
,
Signoretti
,
S.
,
Koivunen
,
P.
, and
Kaelin
,
W. G.
,
2019
, “
Histone Demethylase KDM6A Directly Senses Oxygen to Control Chromatin and Cell Fate
,”
Science
,
363
(
6432
), pp.
1217
1222
.10.1126/science.aaw1026
10.
Michiels
,
C.
,
Tellier
,
C.
, and
Feron
,
O.
,
2016
, “
Cycling Hypoxia: A Key Feature of the Tumor Microenvironment
,”
Biochim. Biophys. Acta BBA - Rev. Cancer
,
1866
(
1
), pp.
76
86
.10.1016/j.bbcan.2016.06.004
11.
Dubois
,
L. J.
,
Niemans
,
R.
,
van Kuijk
,
S. J. A.
,
Panth
,
K. M.
,
Parvathaneni
,
N.-K.
,
Peeters
,
S. G. J. A.
,
Zegers
,
C. M. L.
,
Rekers
,
N. H.
,
van Gisbergen
,
M. W.
,
Biemans
,
R.
,
Lieuwes
,
N. G.
,
Spiegelberg
,
L.
,
Yaromina
,
A.
,
Winum
,
J.-Y.
,
Vooijs
,
M.
, and
Lambin
,
P.
,
2015
, “
New Ways to Image and Target Tumour Hypoxia and Its Molecular Responses
,”
Radiother. Oncol.
,
116
(
3
), pp.
352
357
.10.1016/j.radonc.2015.08.022
12.
Spliethoff
,
J. W.
,
Prevoo
,
W.
,
Meier
,
M. A. J.
,
de Jong
,
J.
,
Klomp
,
H. M.
,
Evers
,
D. J.
,
Sterenborg
,
H. J. C. M.
,
Lucassen
,
G. W.
,
Hendriks
,
B. H. W.
, and
Ruers
,
T. J. M.
,
2016
, “
Real-Time In Vivo Tissue Characterization With Diffuse Reflectance Spectroscopy During Transthoracic Lung Biopsy: A Clinical Feasibility Study
,”
Clin. Cancer Res.
,
22
(
2
), pp.
357
365
.10.1158/1078-0432.CCR-15-0807
13.
Wofbeis
,
O. S.
,
2015
, “
Luminescent Sensing and Imaging of Oxygen: Fierce Competition to the Clark Electrode
,”
Bioassays
,
37
, pp.
921
928
.10.1002/bies.201500002
14.
Vaupel
,
P.
,
Schlenger
,
K.
,
Knoop
,
C.
, and
Hockel
,
M.
,
1991
, “
Oxygenation of Human Tumors: Evaluation of Tissue Oxygen Distribution in Breast Cancers by Computerized O2 Tension Measurements
,”
Cancer Res.
,
51
, pp.
3316
3322
.https://cancerres.aacrjournals.org/content/51/12/3316.long
15.
Linsenmeier
,
R. A.
, and
Yancey
,
C. M.
,
1987
, “
Improved Fabrication of Double-Barreled Recessed Cathode O2 Microelectrodes
,”
J. Appl. Physiol.
,
63
(
6
), pp.
2554
2557
.10.1152/jappl.1987.63.6.2554
16.
Wen
,
B.
,
Urano
,
M.
,
Humm
,
J. L.
,
Seshan
,
V. E.
,
Li
,
G. C.
, and
Ling
,
C. C.
,
2008
, “
Comparison of Helzel and OxyLite Systems in the Measurements of Tumor Partial Oxygen Pressure (pO2
),”
Radiat. Res.
,
169
(
1
), pp.
67
75
.10.1667/RR0888.1
17.
Pucciarelli
,
D.
,
Lengger
,
N.
,
Takáčová
,
M.
,
Csaderova
,
L.
,
Bartosova
,
M.
,
Breiteneder
,
H.
,
Pastorekova
,
S.
, and
Hafner
,
C.
,
2016
, “
Hypoxia Increases the Heterogeneity of Melanoma Cell Populations and Affects the Response to Vemurafenib
,”
Mol. Med. Rep.
,
13
(
4
), pp.
3281
3288
.10.3892/mmr.2016.4888
18.
Konda
,
V.
,
Meining
,
A.
,
Jamil
,
L.
,
Giovannini
,
M.
,
Hwang
,
J.
,
Wallace
,
M.
,
Chang
,
K.
,
Siddiqui
,
U.
,
Hart
,
J.
,
Lo
,
S.
,
Saunders
,
M.
,
Aslanian
,
H.
,
Wroblewski
,
K.
, and
Waxman
,
I.
,
2013
, “
A Pilot Study of In Vivo Identification of Pancreatic Cystic Neoplasms With Needle-Based Confocal Laser Endomicroscopy Under Endosonographic Guidance
,”
Endoscopy
,
45
(
12
), pp.
1006
1013
.10.1055/s-0033-1344714
19.
Arunkumar
,
C.
,
Kooriyaden
,
F. R.
,
Zhang
,
X.
,
Sujatha
,
S.
, and
Zhao
,
J.
,
2017
, “
Fluorinated Meso-Tetraaryl Pt (ii) -Porphyrins: Structure, Photophysical, Electrochemical, and Phosphorescent Oxygen Sensing Studies
,”
New J. Chem.
,
41
(
12
), pp.
4908
4917
.10.1039/C7NJ01141E
20.
Banerjee
,
S.
,
Arzhakova
,
O. V.
,
Dolgova
,
A. A.
, and
Papkovsky
,
D. B.
,
2016
, “
Phosphorescent Oxygen Sensors Produced From Polyolefin Fibres by Solvent-Crazing Method
,”
Sens. Actuators B Chem.
,
230
, pp.
434
441
.10.1016/j.snb.2016.02.062
21.
Briñas
,
R. P.
,
Troxler
,
T.
,
Hochstrasser
,
R. M.
, and
Vinogradov
,
S. A.
,
2005
, “
Phosphorescent Oxygen Sensor With Dendritic Protection and Two-Photon Absorbing Antenna
,”
J. Am. Chem. Soc.
,
127
(
33
), pp.
11851
11862
.10.1021/ja052947c
22.
Chen
,
T.-I.
,
Hsu
,
Y.-C.
,
Lien
,
C.-F.
,
Lin
,
J.-H.
,
Chiu
,
H.-W.
, and
Yang
,
K.-T.
,
2014
, “
Non-Lethal Levels of Oxidative Stress in Response to Short-Term Intermittent Hypoxia Enhance Ca 2+ Handling in Neonatal Rat Cardiomyocytes
,”
Cell. Physiol. Biochem.
,
33
(
2
), pp.
513
527
.10.1159/000358631
23.
Quon
,
G.
, and
Morris
,
Q.
,
2009
, “
ISOLATE: A Computational Strategy for Identifying the Primary Origin of Cancers Using High-Throughput Sequencing
,”
Bioinformatics
,
25
(
21
), pp.
2882
2889
.10.1093/bioinformatics/btp378
24.
Jushiddi
,
M. G.
,
Cahalane
,
R. M.
,
Byrne
,
M.
,
Mani
,
A.
,
Silien
,
C.
,
Tofail
,
S. A. M.
,
Mulvihill
,
J. J. E.
, and
Tiernan
,
P.
,
2020
, “
Bevel Angle Study of Flexible Hollow Needle Insertion Into Biological Mimetic Soft-Gel: Simulation and Experimental Validation
,”
J. Mech. Behav. Biomed. Mater.
,
111
, p.
103896
.10.1016/j.jmbbm.2020.103896
25.
Pervin
,
F.
, and
Chen
,
W. W.
,
2011
, “
Mechanically Similar Gel Simulants for Brain Tissues
,”
Dynamic Behavior of Materials
,
T.
Proulx
ed., Vol. 1,
Springer New York
,
New York
, pp.
9
13
.
26.
Loo
,
J. M.
,
Scherl
,
A.
,
Nguyen
,
A.
,
Man
,
F. Y.
,
Weinberg
,
E.
,
Zeng
,
Z.
,
Saltz
,
L.
,
Paty
,
P. B.
, and
Tavazoie
,
S. F.
,
2015
, “
Extracellular Metabolic Energetics Can Promote Cancer Progression
,”
Cell
,
160
(
3
), pp.
393
406
.10.1016/j.cell.2014.12.018
27.
Gilkes
,
D. M.
,
Semenza
,
G. L.
, and
Wirtz
,
D.
,
2014
, “
Hypoxia and the Extracellular Matrix: Drivers of Tumour Metastasis
,”
Nat. Rev. Cancer
,
14
(
6
), pp.
430
439
.10.1038/nrc3726
28.
Rich
,
L. J.
, and
Seshadri
,
M.
,
2015
, “
Photoacoustic Imaging of Salivary Glands
,”
Biomed. Opt. Express
,
6
(
9
), p.
3157
.10.1364/BOE.6.003157
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