Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT)

Abstract

Microfocus CT (micro-CT) has traditionally been used in industry and preclinical studies, although it may find new applicability in the routine clinical setting. It can provide high-resolution three-dimensional digital imaging data sets to the same level of detail as microscopic examination without the need for tissue dissection. Micro-CT is already enabling non-invasive detailed internal assessment of various tissue specimens, particularly in breast imaging and early gestational fetal autopsy, not previously possible from more conventional modalities such as MRI or CT. In this review, we discuss the technical aspects behind micro-CT image acquisition, how early work with small animal studies have informed our knowledge of human disease and the imaging performed so far on human tissue specimens. We conclude with potential future clinical applications of this novel and emerging technique.

Figure 1.

Microfocus (micro-CT) machine construction principles: (a) a “mini-focus” CT design and a (b) typical micro-CT used for industrial imaging and preclinical research are demonstrated. The mini-focus CT design is similar to that of a medical CT scanner, whereas in the second design the object is being rotated and different parameters such as “source-to-object” and “object-to-detector” distances are adjustable allowing for greater magnification and resolution of the resultant image.

Figure 2.

Inside a microfocus CT machine: the radiation source (X-ray gun), rotating platform (with specimen pot mounted) and detector are visible to the operator and labelled accordingly. All of these components are housed within a radiation-shielding cabinet made of lead and steel, which means there is no need for additional lead shielding when using the machinery, nor for it to be placed in a specialized lead-lined room.

Figure 3.

Microfocus CT imaging of human adamantinomatous craniopharyngioma (ACP): (a) virtual and matched histological tissue section of an ACP showing areas of tumour interspersed by reactive glial tissue. Scale bar indicates 1 mm. (b) 20× images of specific tumour compartments from boxed regions of (a). The left panel shows epithelial whorls (“clusters”) within an area of tumour and the right panel shows “wet keratin” (WK) which has a higher grey value on CT imaging. Scale bars indicate 100 μm. EW, epithelial whorls; G, reactive glial tissue; PE, palisading epithelium; SR, stellate reticulum. Figure adapted from Apps et al under the Creative Commons Attribution License 4.0.

Figure 4.

Microfocus CT volume rendering of a heart and lung block from an 18-gestational week fetus with hypoplastic right heart syndrome: transposition of the great arteries and a ventriculoseptal defect (VSD) can be visualized. Adapted from Hutchinson et al with permission.

Figure 5.

Matched serial microfocus CT (micro-CT) and Movat's pentachrome-stained histological sections: serial micro-CT images (a–d) and corresponding Movat's pentachrome-stained histological sections (e–h) demonstrate the ability of micro-CT to provide sufficient contrast between tissue and paraffin to allow image analysis. RB, respiratory bronchiole; TB, terminal bronchiole. Adapted from Scott et al in accordance with the Creative Commons Attribution License 4.0.

Figure 6.

Contrast-enhanced microfocus CT of fetuses from 7 to 15 weeks of gestation, at resolution of 18 µm: three-dimensional surface rendering is shown on the left, and the internal anatomical details obtained with volume sections are shown on the right. (a) Fetus 1, 7 weeks; (b) Fetus 3, 10 weeks; (c) Fetus 4, 11 weeks; and (d) Fetus 6, 15 weeks. Scale bar in (a) is 1 mm and in (b–d), it is 10 mm. Reproduced from Lombardi et al with permission.