Current methods of assessing tumor response at skeletal sites with metastatic disease use imaging tests, tumor markers, serum and urine biochemical of bone heath, and symptoms assessments. Radiological approaches for metastatic evaluations have specific advantages including their disease manifestation-specific depiction ability (i.e., ability to separately identify/measure local disease, bone, nodal and visceral disease), non-invasive nature, documentation ability, variable ability for whole body imaging, resolution flexibility (sub-millimetre to sub-centimetre), ability to depict physiological and molecular processes, ready access to imaging technologies in many cases and the ability to assess spatial heterogeneity of disease distribution and response.

When multimodal imaging is used to observe bone metastases a number of patterns are observed (table 1). Since single imaging method evaluates metastatic bone disease biology; a comprehensive evaluation requires a multimodal approach to gain an understanding of cancer cell-bone matrix interactions and how that affects appearances (table 2), detection ability and response to therapy.

MRI is a truly multifunctional (non-hybrid) evaluation method for bone metastasis detection and response assessments. Relevant sequences include T1-weighted spin-echo, T2-weighted (with or without fat suppression) and short tau inversion recovery (STIR) which are sensitive to the cellular, fat and water content of the bone marrow. Gradient-echo proton density/T1 sequences using two or three point Dixon techniques (yielding in-phase, opposed phase, water only, fat only, T2* and water and fat fraction images) can be used to objectively evaluate the relative water and fat content of bone marrow. Susceptibility weighted (T2*) sequences are sensitive to spin dephasing induced by trabecular bone. Ultrashort TE (UTE) sequences can also evaluate trabecular bone structure in healthy bone and metastatic disease. A number of studies have evaluated bone marrow vascularisation using DCE-MRI techniques. DWI is also being used because of its sensitivity to bone marrow cellularity, the relative proportions of fat and marrow cells, water content and bone marrow perfusion.

Therapy assessments of bone disease are made by observing changes in the volume and symmetry of signal intensity abnormalities on diffusion weighted images together with changes in ADC values [2]. Cross correlating DW imaging findings with morphological appearances on T1W, fat-saturated T2W/STIR and Dixon F% images is important. Cross correlation with other imaging modalities adds value and confidence to MR image interpretations.

Several distinct patterns being recognized in the therapy assessment setting:

1. Increases in the volume of previously documented abnormal signal intensity, new areas of abnormal signal intensity, or increases in the intensity of abnormalities on high b-value DW images can indicate disease progression. Modest increases, unchanged or slight decreases in ADC values compared to pretherapy values occurs in the setting of progression.

2. T2-shine through - occasionally persistent high signal intensity on high b-value images is associated with marked rises in ADC values is observed. This pattern indicates that there has been a successful response to therapy.

3. Decreases in bone marrow disease signal intensity on high b-value images are generally observed with successful treatments. The extent of ADC increases seems to depend on the type of treatment given. It has been noted that ADC increases are greater for cytotoxic chemotherapy and radiation. When patients are treated successfully with hormonal therapies ADC value increases seem to be less marked. Later on increases in bone marrow fat can be seen within bone marrow lesions indicative of ongoing therapy response. When fat re-emerges in bone marrow lesions, resolution of tumor matrix mineralisation on CT scans can often be seen.

4. Occasionally high b-value signal intensity decreases are associated no ADC increases. Generally this pattern generally occurs in clinical responders although very occasionally we have noted it in non-responders (so called sclerotic progression). These appearances as thus indeterminate and currently we use morphologic and clinical assessments to assign the final response category.

5. Stable disease is characterized by unchanging appearances on high b-value images. ADC changes can be variable, often remaining stable but are sometimes slight decreased presumably because of increases in cell density within lesions that are unchanging in their extent.

Multimodal bone marrow imaging has the potential to address the unmet need for a robust imaging methodology that allows understanding of tumor biology, lesion detection and therapy evaluation of advanced metastatic disease. This means that there is a clearer categorization of bone metastases response (unlike bone scans that only identify disease progression); and more accurate assessments of therapy response (including heterogeneity of response). Multimodal bone imaging could be used for both clinical practice and can be incorporated into clinical trials, generating new biomarkers that in turn will require independent validation.