SYSTEM AND METHOD FOR ENHANCED MASS SPECTROMETRY IMAGING

• US 20170368205A1
• Filed: 12/08/2015
• Published: 12/28/2017
• Est. Priority Date: 12/08/2014
• Status: Active Grant

• Current Assignee: University Health Network
• Original Assignee: University Health Network
• Inventors: Zarrine-Afsar, Arash, Jaffray, David Anthony
• Granted Patent: US 10,441,668 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61K 49/0438 Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
• CPC Class Codes: A61K 49/106 the complex-forming compound being cyclic, e.g. DOTA
• CPC Class Codes: G01N 2458/15 Non-radioactive isotope labels, e.g. for detection by mass spectrometry
• CPC Class Codes: G01N 2560/00 Chemical aspects of mass spectrometric analysis of biological material
• CPC Class Codes: G01N 27/00 Investigating or analysing materials by the use of electric, electrochemical, or magnetic means G01N3/00 – G01N25/00 take precedence; measurement or testing of electric or magnetic variables or of electric or magnetic properties of materials G01R
• CPC Class Codes: G01N 33/4833 of solid biological material, e.g. tissue samples, cell cultures tissue in vivo A61B5/00; cell suspensions G01N33/48735
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence
• CPC Class Codes: H01J 49/0004 Imaging particle spectrometry
• CPC Class Codes: H01J 49/105 using high-frequency excitation, e.g. microwave excitation, Inductively Coupled Plasma [ICP]

Abstract

Various embodiments are described herein for a system and a method for identifying a region of interest in tissue using mass spectrometry. An agent administration component can be provided to administer an exogenous agent to the tissue. A sampling unit can also be provided to acquire a sample from the tissue. The sample can then be provided to a high sensitivity analysis platform, such as a mass analyzer, to analyze the sample and determine a distribution of the exogenous agent or a by-product of the exogenous agent within the tissue based on the analysis. The analysis platform can then identify the region of interest based on the distribution of the exogenous agent or the distribution of the by-product.

Claims

1. A method of identifying a region of interest in tissue, the method comprising:

administering an exogenous agent to the tissue, the exogenous agent being capable of forming a by-product in the tissue;

analyzing a sample based on the tissue using a high sensitivity platform comprising a mass spectrometer;

determining a distribution, optionally quantitative, of the by-product of the exogenous agent within the tissue based on the analysis of the sample; and

identifying the region of interest within the tissue based on the determined distribution of the by-product of the exogenous agent relative to tissue surrounding the region of interest.

2. The method of claim 1, wherein the determining act further comprises determining a distribution of the exogenous agent in addition to the by-product of the exogenous agent.

3. The method of claim 1, wherein prior to the analyzing act the method comprises

acquiring the sample from the tissue after administration of the exogenous agent to the tissue;

and

transporting the sample to the mass spectrometer using a transfer line by applying a positive pressure on the transfer line at a first end proximate to the tissue.

4. The method of claim 3, wherein acquiring the sample comprises desorbing the sample from the tissue, the desorbing act selected from applying laser ablation vaporization, desorption electrospray ionization, or radio frequency ablation.

5. The method of claim 3, further comprising ionizing the sample using inductively-coupled plasma, rapid evaporative ionization, or electrospray ionization prior to analyzing the sample unless the administered exogenous agent includes charged particles, or becomes ionized as an adduct.

6. The method of claim 1, wherein prior to the analyzing act the method comprises obtaining the sample from the tissue using an ex vivo sampling technique.

7. The method of claim 1, wherein the method comprises selecting the exogenous agent so that the at least one of the exogenous agent and the by-product of the exogenous agent has at least one of a mass to charge ratio peak and an elemental mass peak that is not endogenous to the tissue.

8. The method of claim 1, further comprising selecting the agent from chelated metal containing agents and tumour specific metalloporphyrins, or chelated metal containing agents being Gadolinium based, ion oxide based, iron-platinum based, manganese based, or chromium based.

9. The method of claim 1, further comprising selecting the exogenous agent from at least one of a metallic element, a heavy atom, and an isotopic variant that is not endogenous to the tissue;

a metabolic precursor, an isotopic variant of a metabolic precursor, a moiety of a metabolic precursor or a plurality of exogenous sub-agents.

10. The method of claim 9, wherein the at least one isotopic variant comprises an isotopic variant of an endogenous metabolic precursor, and the method comprises determining the distribution of a by-product of the isotopic variant of the endogenous metabolic precursor.

11. The method of claim 1, wherein the exogenous agent is administered encapsulated in a lipidic structure.

12. The method of claim 2, further comprising:

identifying a boundary of the region of interest based on the distribution of at least one of the exogenous agent, and the by-product of the exogenous agent relative to tissue surrounding the region of interest; and

displaying an image of the tissue with the boundary marked.

13. The method of claim 1, wherein the sample comprises a tissue sample, an ablated tissue sample, an ablation plume, a liquefied tissue sample, an extraction of the exogenous agent, or an extraction of the by-product of the exogenous agent.

14. A system for identifying a region of interest in tissue, the system comprising:

a sampling unit configured to acquire a sample based on the tissue after administration of an exogenous agent to the tissue, the exogenous agent being capable of forming a by-product in the tissue; and

a high sensitivity platform comprising a mass spectrometer, the high sensitivity platform being coupled to the sampling unit to analyze the sample, the high sensitivity platform being configured to determine a distribution, optionally quantitative, of a by-product of the exogenous agent within the tissue based on a spectral analysis of the sample to determine spectral peaks due to the by-product of the exogenous agent that are not endogenous to the tissue and, to identify the region of interest based on the determined distribution of the by-product of the exogenous agent relative to tissue surrounding the region of interest.

15. The system of claim 14, wherein the high sensitivity platform is configured to determine a distribution of the exogenous agent in addition to the by-product of the exogenous agent based on a spectral analysis of the sample to determine spectral peaks due to the exogenous agent that are not endogenous to the tissue, and the exogenous agent and the by-product of the exogenous agent having at least one of a mass to charge ratio peak and an elemental mass peak that is not endogenous to the tissue.

19. The system of claim 14, wherein the at least one isotopic variant comprises an isotopic variant of an endogenous metabolic precursor, and the high sensitivity platform is configured to determine the distribution of a by-product of the isotopic variant of the endogenous metabolic precursor.

21. The system of claim 14, wherein the sampling unit comprises at least one of a desorption component configured to desorb the sample from the tissue, a vaporization component configured to vaporize the sample from the tissue, the desorption component comprises a laser ablation device;

and an ionization device configured to ionize the sample from the tissue the ionization device comprising an inductively-coupled plasma ionization device.

23. The system of claim 14, further comprising a transportation unit including a transfer line that is configured to couple the sampling unit and the mass spectrometer to transport the sample to the mass analyzer unit and the transfer line is configured to apply a positive pressure on the transfer line at, a first end of the transfer line, the first end being proximate the tissue from which the sample is acquired.

24. The system of claim 23, wherein at least one of the sampling unit and the transfer line comprises trackable markings;

and the high sensitivity platform is configured to track the trackable markings to identify a location of the tissue where the sample was acquired.

26. The system of claim 21, further comprising a transportation unit including a transfer line configured to couple the sampling unit and the mass spectrometer to transport the sample to the mass analyzer unit, wherein the transfer line houses the at least one of the desorption component and the vaporization component.

27. The system of claim 14, further comprising a display device;

wherein the high sensitivity platform is further configured to identity a boundary of the region of interest; and

the display device is configured to display an image of the tissue with the boundary marked.

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