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
|