January 1999 - techniques

• Diffraction reaches the parts other Medical tests fail to reach

Diffraction reaches the parts oth er Medical tests fail to reach

The human body is a complex, dynamic biological system which is, at best, poorly understood. Fortunately for crystallographers, much of our tissues contain significant amounts of crystalline or semi-crystalline materials. In many cases, the nature of these materials can provide information that enables us to study ageing and disease processes. Further, with the development of improved data collec tion and analysis methods, diffraction has started to provide doctors with some disease diagnoses.

The most frequently formed biological mineral is a calcium salt usually approximated by hexagonal calcium hydroxyapatite (HAP) which constitutes the majority inorganic material of bone and teeth. However, tissue deposition of other calcium phases are also associated with a wide range of significant medical problems such as breast cancer, renal disease, atherosclerosis bioprosthetic heart valv e failure and arthritis.

Generally, biological minerals have a small crystallite size (specific surface areas are typically >100 m²g^-1), are non-stoichiometric (apatite comes from the Greek word deceive), and show extensive inheterogeneity. A major challenge for the diffractionist is significant overlapping of broad Bragg maxima. This has resulted in many analysts choosing to utilise only a very limited part of the diffraction patterns (often 1 peak) t o characterise the materials. However, application of techniques such as the Rietveld method is allowing more structural details to be revealed.

Diagnosing breast cancer

Breast tissue is an unusually dynamic system with respect to the deposition of biological minerals. Radiologists frequently utilise the radiographic appearance of breast tissue mineral deposits as a 'first line' diagnostic tool for signs of malignant change. Despite this, the precise nature of these deposits is unclear, although a common misconception is that only HAP and a calcium oxalate are formed. Pathologists often correlate these two phases to the tumour type, but do not use diffraction to provide the phase determination, instead relying on non-phase specific methods such as staining. There is some evidence that there is a wide range of phases formed and that the phase sensitively reflects tissue pathophysiology e.g. be a marker for tumour grade & type. Recently, small angle X-ray scattering has been used to demonstrate a significant difference in the structural order of tumour collagen when compared to adjacent tissue. This may lead to a simple, in vivo test for malignant tumours based upon the coherent scattering that is currently disregarded by the radiologist when producing a mammogram.

Characterising bone

Bone is a composite material that is continuously remodelled throughout life. The mineral component resembles HAP, and possesses key functional characteri stics such as crystallite size, stoichiometry and preferred orientation. These characteristics are known to change with age and in response to diseases such as osteoporosis. Interestingly, bone mineral texture has also shown evolutionary, adaptive changes that result in modification of bone mechanical properties. It should be appreciated that complete crystallographic interpretation of diffraction data from human bone mineral remains rare. Indeed the precise nature of the mineral is still a matter o f some conjecture.

Kidney stone architecture

Most 'normal' humans produce some crystalline material within their urine. A significant medical question is why in some people these crystals go on to form stones before they can be excreted. In fact, agglomerations of relatively large mineral crystals can be found in many parts of the urinary system. The nature of the many (>20) minerals found within urinary stones was determined in the 1960 ' s. However, current medical interest focuses upon the detail of the internal stone architecture (crystal growth/agglomeration patterns) so that new treatments e.g. laser lithotripsy, can be optimised. Also it is hoped that pre-treatment diagnosis of the stone type being formed may be acquired from the diffraction data of 'urine debris'.

Sadly, the potential of diffraction to provide diagnosis or fundamental data is grossly under exploited by the medical community. However, a hope is that the use of diffraction will, in futur e, become an invaluable medical tool. Have a good look at the equipment next time you are unfortunate enough to be in hospital - there may just be a diffractometer next to the ECG machine!

Keith Rogers