Current and Developing Lymphatic Imaging Approaches for Elucidation of Functional Mechanisms and Disease Progression

Figures

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  Fig. 1. Academic Interest in lymphatics and lymphatic imaging from 1945 to 2021 in the PubMed Database. A) New entries for “lymphatic” (plotted in grey) and “lymphatic imaging” (plotted in black)

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  Fig. 2. Initial lymphatic features of meningeal lymphatic vessels. a Representative images of CCL21 and Lyve-1 labeling of the meningeal lymphatic vessels (scale bars, 10 μm). b, c Representative images of VE-Cadherin and Lyve-1 staining on meningeal blood vessels (b) and meningeal lymphatic vessels (c), arrowheads point to the VE-Cadherin aggregates; scale bars, 10 μm. (Adapted with permission from Louveau et al., 2015, ©2015, Nature published by Springer Nature)

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  Fig. 3. a Representative images of MOG-specific T cells (2D2) and OVA-specific T cells (OTII) in the dCLNs of mice treated with laser and Visudyne (i.c.m.) + laser at day 8 after EAE induction. Green arrowheads, OTII T cells. Yellow arrowheads, 2D2 cells not in contact with CD11c+ cells; white arrowheads, 2D2 cells in contact with CD11c+ cells. Scale bar, 150 μm; insets, 25 μm. Representative of 5 independent mice per group. b Representative images and associated profile plots of MOG-specific T cells (2D2, red) in close contact (top) or not in contact (bottom) with CD11c+ cells (cyan) in the dCLNs of mice treated with laser and Visudyne (i.c.m.) + laser 8 d after EAE induction. Scale bar, 10 μm. Representative of 5 independent mice per group. (Adapted with permission from Louveau et al., 2018, ©2018, Nature Neuroscience published by Springer Nature)

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  Fig. 4. a Traditional lymphoscintigraphy shows the consequences of extensive inguinoiliac lymphadenodysplasia (the inguino-iliac lymph nodes are not visible, arrow 5 on the right side with the tracer flowing into lymphatic vessels and the superficial lymphatic collateralization network up to the root of the limb. Arrows with L indicate the liver, wherein radiocolloids are taken up when they have reached the systemic circulation. (Adapted with permission from Roman et al., 2018, ©2018, World Journal of Surgical Oncology published by Springer Nature) b T1-weighted gradient echo MRI maximum intensity projection image of a 55-year-old woman with a history of ovarian cancer and pelvic lymphadenectomy who presented with right leg edema. After intracutaneous administration of a contrast agent into the web spaces of the right foot MRI imaging reveals a large lymphatic channel ascending the anterior calf and dermal backflow to the medial upper calf (arrowhead). Dermal backflow is intermittently identified with MRI in some patients with secondary lymphedema. Note the increase in spatial resolution as compared with lymphoscintigraphy. (Adapted with permission from Lee et al., 2022, ©2022,…

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  Fig. 5. Comparative images between traditional lymphoscintigraphy (LS) and photoacoustic imaging (PAI). Dermal backflow (DBF) was visualized similarly using both techniques. Both show representative cases of type 3 lymphedema with dermal back flow in the early phase of lymphoscintigraphy. Each DBF is surrounded by a square, and the linear lymphatic vessels proximal and distal to it (arrows) can be seen in both examinations. (Adapted with permission from Watanabe et al., 2022, ©2022, Journal of Vascular Surgery: Venous Lymphatic Disorders, published by Elsevier)

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  Fig. 6. a Whole body coronal PET/MRI fused slice of [89] Zr-ferumoxytol in a draining lymph node, 6 h post-injection. b Magnified prostate region distinctly shows that the draining LN is outside of the prostate organ. The ventral prostate in this slice is delineated by a dashed green outline. c In the reconstructed axial orientation (located at the hashed marks on the coronal image), sensitive PET detection enables visualization of tracer in a more distant draining inguinal node (red arrow). In the clinical context, the detection of a draining LN outside of the pelvic bed would necessitate a widened field of biopsy sampling or therapeutic intervention. All scale bars are 0.8 cm in length. (Adapted with permission from Thorek et al., 2014, ©2014, Nature Communications, published by Springer Nature)

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  Fig. 7. 3D PET-CT fusion maximum intensity projection images integrated 18F-FDG and 124I-cRGDY-PEG-C dot PET-CT. a In the 18F-FDG PET-CT fusion image (coronal view) there is no evident nodal metastases (asterisks). Increased activity within bony structures is identified. b, c In contrast to the 18F-FDG image, the 124I-cRGDY-PEG-C-dot high-resolution PET-CT fusion images show coronal (b) and superior views (c) of bilateral metastatic nodes (open arrows) and lymphatic channels (curved arrows) within the neck following local injection of 124I-cRGDY-PEG-C dots. (Adapted with permission from Bradbury et al., 2013, ©2013, Integrative Biology, published by Oxford Academic)