Chapter 7 – Complementary Experimental Tools  305

local physicochemical environment surrounding that atom and is thus a sensitive metric for

probing tissue heterogeneity.

By moving the sample perpendicularly to the xy lateral sampling plane along the cen­

tral z-​axis of the scanner, full 3D xyz spatial maps can be reconstructed, with total scan

times of a few tens of minutes. Diagnostic MRI can be used to discriminate relatively subtle

differences in soft tissues that have similar x-​ray attenuation coefficients and thus can reveal

tissue heterogeneities not observed using CAT/​CT scanning (see in the following text), for

example, to diagnose deep tissue mechanical damage as well as small malignant tumors in a

soft tissue environment.

MRI can also be used for functional imaging, defined as a method in biomedical imaging

that can detect dynamic changes in metabolism. For MRI, this is often referred to as func­

tional MRI (fMRI). The best example of this is in monitoring of blood flow, for example,

through the heart and major blood vessels, and to achieve this, a contrast reagent is nor­

mally applied to improve the discrimination of the fast-​flowing blood against the soft tissues

of the walls of the heart and the blood vessels, usually a paramagnetic compound such as a

gadolinium-​containing compound, which can be injected into the body via a suitable vein.

The spatial resolution of the best conventional MRI is limited to a few tens of microns and

so in principle is capable of resolving many individual cell types. However, a new research

technique called nitrogen vacancy MRI is showing potential for spatial resolution at the

nanometer scale (see Grinolds et al., 2014), though it is at too early a stage in development to

be clinically relevant.

7.8.2  X-​RAYS AND COMPUTER-​ASSISTED (OR COMPUTERIZED) TOMOGRAPHY

Ionizing radiation is so called because it carries sufficient energy to remove electrons from

atomic and molecular orbitals in a sample. Well-​known examples of ionizing radiation include

alpha particles (i.e., helium nuclei) and beta radiation (high-​energy electrons), but also x-​rays

(photons of typical wavelength ~10⁻¹⁰ m generated from electronic orbital transitions) and

gamma rays (higher energy photons of typical wavelengths <10⁻¹¹ m generated from atomic

nucleus energy state transitions), which are discussed in Chapter 5. All are harmful to bio­

logical tissue to some extent. X-​rays were historically the most biomedically relevant, in that

hard tissues such as the bone in particular have significantly larger attenuation coefficients

for x-​rays compared to that of soft tissues, and so the use of x-​rays in forming relatively simple

2D images of the transmitted x-​rays through a sample of tissue has grown to be very useful

and is the standard technique used for clinical diagnosis.

Thus, T-​rays (i.e., terahertz radiation) can be used in a similar way to x-​rays for discrim­

inating between soft and hard biological tissues (see Chapter 5). However, T-​rays have a

marginal advantage when specifically probing fine differences in water content between one

tissue and another. These differences have been exploited for the detection of forms of epi­

thelial cancer. But also, T-​rays have been applied in generating images of the teeth. However,

the widespread application of T-​rays biomedically is more limited because of the lack of

availability of commercial, portable T-​ray sources and so is currently confined to research

applications.

CAT or CT, also known as computerized tomography, involves scanners that utilize x-​ray

imaging but scan around a sample using a similar annulus scanner/​emitter geometry to MRI

scanners, resulting in a 2D x-​ray tomogram of the sample in the lateral xy plane. As with MRI,

the sample can be moved perpendicularly to the xy sampling plane along the central z-​axis of

the scanner, to generate different 2D tomograms at different incremental values of z, which

can then be used to reconstruct full 3D xyz spatial maps of x-​ray attenuation coefficients

using offline interpolation software, representing a 3D map of different tissue features, with

similar scan times. The best spatial resolution of commercial clinical systems is, in principle,

a few hundred microns, in other words limited to a clump of a few cells. This is clinically very

useful for diagnosing a variety of different disorders, for example, cancer, though in prac­

tice the smallest tumor that can be typically detected reliably in a soft tissue environment is

~2 cm in diameter.