TABLE 1.
Current and potential biomedicaL applications of PARS and PACT.
| Application | Cleared tissue | Additional references |
|---|---|---|
| Biodistribution of chemicals or biologicals (e.g., virus infectivity, antibody and gene therapies) | Whole-body clearing (Fig. 1a–e) | 143 – 150 |
| Mapping discrete cellular niches, such as 3D genetic makeup and architecture of tumors, stem cell niches; potential for larger volume array tomography151,152 | PACT of tumor biopsies18 and whole-body PARS for rodent cancer models | 98,101, 153–157 |
| Monitoring the progression of cell death and tissue damage (i.e., in stroke, peripheral infarcts), and the corresponding neurogenesis | PARS for whole-body, targeted vasculature fixation and immunolabeling | 158,159 |
| Tract tracing complex long-range fiber bundles (e.g., vagus nerve) and whole-body vasculature (i.e., both circulatory and lymphatic systems); short- and long-range cellular 3D mapping160 (including via neuronal positioning system (NPS)133, via Brainbow161 and via array tomography151,152) | PARS with whole-body targeted IHC, PARS-CSF (spinal cord), PACT-deCAL for vertebral column, ePACT for subcellular spectral resolution of overlapping NPS vesicles, Brainbow labeling and FISH probes | 39–41,133, 162–164 |
| Following neurodevelopment (neural stem cell differentiation), neurogenesis and nerve/axon regeneration | PARS | 14,165–169 |
| Tracking myelination trajectory over lifetime and demyelination in disease states (autism, traumatic brain injury, multiple sclerosis) | PACT and PARS with IHC for myelin-associated proteins and markers of inflammation (Fig. 5d) | 165,170–173 |
| Studying the brain-gut connection, microbiome, blood-brain barrier permeability | PARS | 174,175 |
| Assessing the effects of peripheral immunoactivation on cognition and health | PARS with IHC for cytokines, inflammation and neuronal markers | 171,172,176 |
| Imaging through dense, complex tissues (e.g., bone marrow stem cells) | PACT-deCAL for through-bone labeling and imaging | 97,164, 177–182 |
| Exploring topics in microbiology, including biofilms (characterizing biofilm structure and the interaction of different cellular layers), the heterogeneity and distribution of microbes that occupy the same niche | PACT with considerations for fragile samples (e.g., PACT-hydrogel formulated with paraformaldehyde and/or bis-acrylamide) so that bacterial colonies are retained in tissue or biofilm samples during clearing | 183 – 186 |
| Diffusion tensor imaging (DTI)187 and spectral confocal reflectance microscopy (SCoRe, for label-free in vivo imaging of myelinated axons)188 | Future potential for ex vivo variation of DTI, wherein PARS-based diffusion of materials and immunolabels grants whole-organism imaging | 166,188–191 |