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Doctoral Committee

Scheme 4: A) Synthesis of complex 5B, (B) Optimised structure of the complex with two inner sphere water molecules

1.1 Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging (MRI) has become an indispensable medical technique since the pioneering work by Paul Lauterbur, the father of MRI, in the 1970s.1 The idea of developing images from the Nuclear Magnetic Resonance (NMR) signals leads to the discovery of this very useful technique for non‒invasively peering inside the body and allowing the detection of a variety of physical abnormalities. Unlike other imaging techniques, MRI does not use any harmful radiation that can be harmful to the tissues.2 So, MRI is the best method to characterise and discriminate among the tissues using their physical and biochemical properties.

Including cerebrospinal fluid and blood flow detection, contraction and relaxation of the organs, most of the physiological and pathological phenomena can be evaluated by using MRI which cannot be done by other imaging techniques like standard X‒rays, Computed Tomography scan (CT scan), or Ultrasound.

The practice of generating images with MRI was developed from the same principles which govern routine Nuclear Magnetic Resonance (NMR) spectroscopy commonly used as a characterisation technique in organic synthesis.3 A typical MRI scanner is comparable to that of a standard NMR spectrometer used for structural characterisation of a sample prepared in a relatively small tube. MRI, however, employs only the water proton signal in a much larger human ‘sample’ and relies on the abundant water distribution throughout tissue and magnetic field gradients in different directions to generate the image. Figure 1.1 shows a basic setup of a typical MRI scanner.

Figure 1.1. Basic setup of a typical MRI scanner.4

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MRI scanner (Figure 1.1) consists of a super conducting magnet, which creates a homogeneous strong magnetic field, a radio frequency coil, and a gradient coil, surrounding the patient. A receiver coil is also present in the system, which is connected to an external computer.

The computer receives the signals and processes the signals into images.

Human body is primarily consists of fat and water, which make the whole body approximately with 70% water.5 MRI thus images the NMR signals of the hydrogen nuclei of these water molecules. The proton nuclear spins of these water molecules are constantly in spinning motion creating a magnetic field and they are randomly oriented in the absence an external magnetic field (Figure 1.2). Once they are placed in an external magnetic field (Figure 1.2), they align themselves either parallel or antiparallel to the magnetic field. The preferred state of alignment is the one that needs less energy. So, more protons are on the lower energy level, parallel to the external magnetic field. However, the difference in number is very small and depends on the strength of the applied magnetic field.

Figure 1.2. Protons in the (A) absence and (B) presence of magnetic field.

In addition to alignment of nuclei with a magnetic moment, application of an external magnetic field will produce a secondary spin or wobble of nuclei around the main or static magnetic field. This precessional path around the magnetic field is circular like a spinning top and the frequency is called Larmor frequency. This is the frequency with which the proton nuclear spin absorb the energy. When a radio frequency pulse at this Larmor frequency is applied, two things may happen: some of the proton spins flip to the opposite direction of the magnetic field, and the protons get synchronised, start to precess in phase. When the external radiofrequency signal is turned off, the protons which are in opposite direction of the magnetic field, return to their equilibrium positions with the loss of energy to the surrounding nuclei; and

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the protons which precess in phase, lose phase coherence and they get out of phase. These phenomena are called relaxation.

Two ways of returning back to the equilibrium positions are:

1) Longitudinal relaxation or T1 relaxation, and 2) Transverse relaxation or T2 relaxation

Longitudinal relaxation is also called spin‒lattice relaxation where relaxation takes place along the direction of the magnetic field or this is the relaxation time for the magnetization to return to 63% of its original value. The net magnetization Mz along the z‒axis after time ‘t’ is given by the equation:

M

z(t)

= M

z(0)

(1 – e

–t/T1

)

where T1 is the longitudinal relaxation time.

Figure 1.3. Change in magnetization along z–axis.

Figure 1.4. Decay in magnetization along xy‒plane.

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Transverse relaxation is also called spin‒spin relaxation which is the time taken to disappear 69% of the magnetization along its transverse plane. The decay of the transverse magnetization along xy‒plane is given by the equation:

M

xy(t)

= M

xy(0)

e

–t/T2

where Mxy(t) is the transverse magnetization after time ‘t’, and T2 is the transverse relaxation time.

The T1 and T2 relaxation times are dependent on the local environment of the water molecules. The discovery of the fact; different types of biological tissues have different relaxation times, led to design the MRI machine, which can detect the internal malignancies.

Table 1.1. T1 Relaxation times of some malignant and normal tissues:6 Tissue T1 Tumar (s) T1 Normal (s)

Liver Spleen

Lung Skin Stomach

Breast Bone

0.832 1.113 1.110 1.047 1.238 1.080 1.027

0.570 0.701 0.788 0.616 0.765 0.367 0.554

Tissues which have shorter T1 values provide brighter image intensity as the magnetization along z‒axis becomes high with the faster relaxation process. On the other hand, short T2 values are always associated with lower signal intensity since it diminishes the net transverse magnetization available for detection.

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