Length Scale Matters: Real-Time Elastography versus Nanomechanical Profiling by Atomic Force Microscopy for the Diagnosis of Breast Lesions

Figure 4

Stiffness sensitivity and spatial resolution of nanomechanical testing improves diagnostic accuracy. (a) (Top) Fibroadenoma: in B-mode image, oval circumscribed hypoechogenic lesion of 5.1mm diameter with a BI-RADS score of 3. The even strain in the lesion and in the surrounding tissue at a strain ratio of 5.18 led to a Tsukuba score of 5 (malignant). Histology revealed this false positive. (Middle) In contrast to elastography, the high spatial and force sensitivity of the AFM allowed for a clear distinction of the cellular and extracellular matrix (ECM) components. The biopsy-wide histogram reveals a broad stiffness distribution up to 20 kPa arising from the stiff ECM components with a prominent peak around 2 kPa that is correlated well with the high glandular content in the lesion as corroborated by the post-AFM histology image (bottom). Scale bar, 200 μm. (b) (Top) Invasive ductal breast cancer: B-mode image shows an irregular hypoechogenic lesion of 21 mm diameter with architectural distortion, assigned a BI-RADS score of 5. RTE reveals a lesion of little strain reflected by a mosaic pattern of blue and dominantly green in the elastogram assigned a Tsukuba score of 2 (false negative score) (strain ratio 0.33). (Middle) The biopsy-wide histogram of AFM stiffness recordings reveals a bimodal stiffness distribution typical for invasive breast cancer. The prominent and narrow stiffness peak dominating at 0.6 kPa is a feature of cancer cells. (Bottom) Post-AFM histology shows large areas with densely packed cancer cells and low stromal content being present in the biopsy, which might explain the strain ratio and false Tsukuba score. Scale bar, 200 μm.