Tiempo de concentración (Tc)

This has been performed initially in normal tissues such as the liver, pancreas and colon. The nature and extent o f laser m ediated tissue damage, temperature gradients created, their relationship to different laser parameters and structural and functional changes in treated organs have been studied. In addition, the mechanism and time scale o f healing o f treated tissue and any untoward effects associated with treatment acutely and in the long term and how these relate to treatment parameters and fibre position have been evaluated. Attempts have been made to evaluate the influence o f ILH on survival in animal tumour models by determining the laser parameters which equate with complete necrosis and safe healing.

Imaging is an important and complementary aspect o f ILH as its biological effect cannot be reliably assessed visually. So far, U S has attracted the most attention as a

potentially easy to use, cheap and simple imaging modality which does not utilise ionising radiation. Experimental work has attempted to correlate real time and end treatment images with macroscopic and m icroscopic extent o f tissue necrosis. Clearly, such studies are fundamental to the successful clinical application o f ILH. Other workers have pursued the technical aspects o f laser delivery systems, especially fibre tip design inorder to maximise the biological effect o f ILH for a given treatment energy. It is this aspect o f experimental work I shall start with before going on to consider specific organs.

3.2.1 DELIVERY SYSTEMS

Interstitial laser light delivery systems have been investigated using 3 main fibre types. A bare fibre optic, where the plastic cladding has been removed exposing the light transmitting quartz or glass fibre is the sim plest arrangement. An alternative is to use diffuser fibres which in theory provide more uniform light irradiation o f the tissue producing a more homogeneous biological effect. Lastly, the versatility o f sapphire tips which can be coupled to a bare quartz fibre has attracted a lot o f attention. The tip geometry can be selected to enhance a particular biological effect such as cutting or coagulation.

Van Eeden (1988) investigated variation in maximum extent of necrosis in liver. Using a bare quartz fibre, he altered the fibre diameter, fibre tip configuration and depth o f entry o f laser light both in-vitro and in-vivo. Comparison between 400 and 600 micron quartz fibres for a given treatment energy produced no significant difference in the extent o f necrosis. Altering the fibre tip o f a bare 600 micron fibre by etching the tip with hydrofluoric acid (a simple diffuser effect is produced), or attaching a sapphire probe did not produce a useful benefit over simple cleavage and removal o f the plastic cladding. It was noted that the optimum depth for maximum thermal necrosis in vivo and in vitro for a given treatment energy is 5 to 10 mm.

Hashimoto et al (1985), in a clinical feasibility study treated patients with liver cancer using powers o f 5 to 15 watts from a Nd:YAG laser coupled to a laser fibre with a modified quartz diffuser tip. Preliminary results indicate successful induction o f tumour necrosis although the extent o f necrosis is not specified. W hile allowing more uniform tissue irradiation, the power density from a diffuser fibre is likely to be low at the tip-tissue

interface. This may prevent tissue carbonization due to excessive temperatures around the fibre tip. However, power densities maybe insufficient for adequate coagulation o f large tissue volumes. In m ost instances, self heating o f the diffusing m icrodom e lim its laser powers to only 1 watt.

Sapphire tips are w idely used in a variety o f clinical laser applications. Their attraction stems from geometric modifications made to the sapphire to tailor the power density to a desired biological effect. U sing a chiselled probe generates very high power densities at the tip with very little scattering into non-targeted tissues. This allow s very precise tissue cutting. A broader sapphire tip lowers the power density considerably due to increased interaction surface area. A s a result, the predominant b iological effect is coagulation. However, Sapphire tips are not without their problems. Using an end on and an integrated sphere power meter, Steger et al (1988) demonstrated a 30-50% loss o f the input power at the sapphire tip. Direct thermometery demonstrated a 50 to 60^C rise at the junction o f the proximal sapphire end and metal connector compared to its distal end. A plausible explanation is that a proportion o f laser light is probably reflected back from the proximal sapphire surface to be absorbed by the metal connector causing it to heat up. A third to one half o f the input laser energy contributes to this effect and, in essence, makes the sapphire tip act more like a hot probe rendering the biological effect less predictable. This phenomenon has two undesirable effects. For equivalent laser energies, the diameter o f necrosis using a sapphire tip is significantly smaller than with a bare fibre while co-axial water or gas is needed to cool the collar assembly. Fatal air emboli have been associated with gas cooling during gynaecological procedures following inadvertent entry o f air into a vein. In addition, the width o f sapphire tips and the metal collar required to fix them to the laser fibre makes them impractical for percutaneous use.

The low powers necessary for ILH mean prolonged treatment times when treating large tissue volumes. The logical answer is to attempt to increase the laser power, however, diffu sin g quartz fibres and sapphire probes are unsuitable for high pow er photocoagulation. In an attempt to overcome this problem, Godlewski (1988) developed a device for inducing deep focal tissue necrosis and vaporisation using a N diY A G laser at high powers (100 Watts). This consisted o f a large proximal base attached to an axial

channel which allows the passage o f a laser fibre with two lateral ducts for a cooling circuit. Within the axial channel, a disposable sheath (200 mm long with a diameter of 5 mm) which houses the bare fibre and cooling circuit. The distal end o f the sheath is closed by a window through which the laser beam is transmitted. The w indow and fibre are cooled by circulating water. This device was used at laparotomy on porcine liver with a 6 mm trocar to allow the device to be introduced into the liver substance. Treatment parameters consisted o f ten 1 second exposures at a power o f 100 Watts. One hour from treatment, ultrasound examination revealed a central echo free area corresponding to the central charred cavity with a circumferential hyperechoeic pattern denoting necrotic but non­ vaporised tissue. By the third to tenth day, these features were w ell demonstrated, in addition, a further hypoechogenic halo o f oedema gave a characteristic bull's eye appearance. Post mortem analysis 3 days from treatment showed a well defined spherical area of tissue necrosis up to 18 mm in diameter (range 12 to 18 mm) with a central zone o f cavitation and charring 5 to 8 mm in diameter. The animals showed no ill effects from their treatment with all treated sites healing by scarring within 4 months from treatment. However, at no stage was any attempt made to correlate the ultrasound assessment and post mortem evaluation o f the extent o f necrosis nor study the effect o f lower laser powers on the extent o f necrosis. A major drawback to this approach is the rapidity o f energy delivery and ensuing biological effect making it im possible to study the evolution o f thermal changes in real time. Sonographic assessment o f the biological effect can only be made once the damage is done be it to targeted or non-targeted tissue. This m akes for poor control o f the extent o f tissue necrosis with possible inadvertent tissue damage. Clearly, the dimensions o f Godlewski's device make impractical for percutaneous use. If this technique is to offer any useful advance, a compromise has to be made between short exposure times / high powers and control over the biological effect.

Sophisticated delivery systems which monitor temperature and light distribution during laser photocoagulation have been reported. Daikuzono and his colleagues (1988) developed a new computer controlled NdiYAG system which interfaces with temperature probes placed within the treated tissue. This is more fully discussed later in this chapter.

Almost all reports in the field o f laser hyperthermia have utilised single laser fibres with or without modification. The concept o f a multi fibre delivery system is theoretically an attractive one allowing a single laser to simultaneously produce clinically useful powers o f equal intensity down 2 or more fibres. This topic is further discussed in the next section.

3.2.2 ORGAN STUDIES I) Li v e r

Matthewson et al (1987) provided som e o f the best documented results on ILH using much lower powers than Godlewski. The experimental model consisted o f exposing the left lobe o f the rat liver at laparotomy which was irradiated using a single 400 micron diameter fibre inserted interstitially. The liver was photocoagulated using a range o f laser powers (0.5 to 2.0 watts) from a NdiYAG laser with varying exposure times (100 to 1000 seconds). The animals were killed 3 to 4 days from treatment to evaluate the extent o f necrosis. The results allowed the following conclusions to be made.

1. Well defined areas o f necrosis, roughly spherical in shape and up to 16 mm in diameter