Terahertz in-line digital holography of human hepatocellular carcinoma tissue

Abstract

Terahertz waves provide a better contrast in imaging soft biomedical tissues than X-rays, and unlike X-rays, they cause no ionisation damage, making them a good option for biomedical imaging. Terahertz absorption imaging has conventionally been used for cancer diagnosis. However, the absorption properties of a cancerous sample are influenced by two opposing factors: an increase in absorption due to a higher degree of hydration and a decrease in absorption due to structural changes. It is therefore difficult to diagnose cancer from an absorption image. Phase imaging can thus be critical for diagnostics. We demonstrate imaging of the absorption and phase-shift distributions of 3.2 mm × 2.3 mm × 30-μm-thick human hepatocellular carcinoma tissue by continuous-wave terahertz digital in-line holography. The acquisition time of a few seconds for a single in-line hologram is much shorter than that of other terahertz diagnostic techniques, and future detectors will allow acquisition of meaningful holograms without sample dehydration. The resolution of the reconstructions was enhanced by sub-pixel shifting and extrapolation. Another advantage of this technique is its relaxed minimal sample size limitation. The fibrosis indicated in the phase distribution demonstrates the potential of terahertz holographic imaging to obtain a more objective, early diagnosis of cancer.

Figure 1. Schematic layout of the setup for continuous-wave terahertz in-line digital holography.

An output terahertz laser beam of 11 mm in diameter was expanded to 22 mm in diameter by using two gold-coated off-axis parabolic mirrors, PM1 and PM2, with effective focal lengths of 76.2 mm and 152.4 mm, respectively.

Figure 2. Terahertz in-line hologram of the steel blade of a screwdriver and its reconstructions.

(a), photo of the metal blade. (b), normalised hologram. (c), reconstructed absorption distribution a(x,y). (d), reconstructed phase-shift distribution φ(x,y). (e–f), reconstructed absorption and phase distributions after 100 iterations, respectively.

Figure 3. Terahertz in-line hologram of human hepatocellular carcinoma tissue and its reconstructions.

(a), photo of the sample after holographic data acquisition. (b), normalised hologram obtained at a selected detector position; the hologram size is 12.4 × 12.4 mm² sampled with 124 × 124 pixels. (c), reconstructed absorption distribution a(x,y). (d), reconstructed phase-shift distribution φ(x,y).

Figure 4. Upsampled holograms of human hepatocellular carcinoma tissue and their reconstructions.

(a), normalised hologram. (b–c), object absorption and phase-shift distributions reconstructed from the normalised hologram. The absorption up to a = 0.22 a.u. means that up to 36.21% of the incident radiation was absorbed. (d–e), reconstructed absorption and phase-shift distributions after 200 iterations, respectively. (f), extrapolated hologram after 200 iterations. (g), the amplitude of the complex-valued field at the detector after the last iteration. (h–i), absorption and phase-shift distributions reconstructed from the extrapolated hologram.

Figure 5. Terahertz in-line hologram of human healthy liver tissue and its reconstructions.

(a), photo of the sample after holographic data acquisition. (b), normalised hologram. (c–d), object absorption and phase-shift distributions reconstructed from the normalised hologram. (e–f), absorption and phase-shift distributions reconstructed from Fig. 5(b) after 200 iterations, respectively. (g–h), absorption and phase-shift distributions reconstructed from the extrapolated hologram.

Figure 6. Terahertz in-line holograms of mouse healthy liver tissue and their reconstructions.

(a), normalised hologram from the first 100 frames of 1,000 frames in total. (b–c), object absorption and phase-shift distributions reconstructed from Fig. 6(a). (d), normalised hologram from the last 100 frames of the 1,000 frames. (e–f), absorption and phase-shift distributions reconstructed from Fig. 6(d). The rings in the reconstructions are due to the applied round cosine-like apodisation filter, which sets the intensity values at the holograms' edges to zero, as seen in (a)and (d), to avoid reflection of the signal at the edges of the holograms during Fourier transforms.