Ed1 s20 md

For the in-vitro experiment, the handheld LSCI system was mounted on a translational stage facing perpendicular to a Delrin plate and a linear speed range of $V=[0,10]$  mm/s during 10.35 s was applied. An example of this experiment is shown in Supplementary Video S5 for an exposure time of $T=10\mathrm{ms}$ .
Similarly, for the in-vivo experiments, that were performed before usage in psoriasis patients, the LSCI system was mounted on a translational stage to which a linear speed range of $V=[0,10]$  mm/s during 3.3 s was applied. The study consisted of two phases. In the first phase, the skin had a normal perfusion level. In the second phase, the measurement was carried out 15 min after applying 0.2 ml vasodilating cream (60 gr Midalgan cream Extra Warm, Qualiphar, Meppel, The Netherlands) on an area of $20\mathrm{cm}\times 5\mathrm{cm}$ . The second phase is referred to as ‘high perfusion level’.
For both the in-vitro and in-vivo experiments, a ${20}^{\circ }$ top hat engineered diffuser (Thorlabs ED1-S20-MD) with square scattered shape was used to expand the laser beam. The speckle frames were captured with an exposure time of $T=25\mathrm{ms}$ , a frame rate of 40 Hz and a gain of 0 dB. The speckle contrast for each captured frame was calculated from a windows of size $150\mathrm{px}\times 150$  px.

A custom-built setup consisting of a fiber (200 µm core) coupled 793 nm laser (20 W, Lumics LU0793D140-D10DH) was used. The laser is launched in an excitation cube by the fiber and reflected through a mirror (Thorlabs BBE1-E03). The reflected light is passed through a positive achromat (Thorlabs AC254-050-B) to an engineered diffuser (Thorlabs ED1-S20-MD) to provide a uniform illumination over the working area. The average excitation flux at the animal was close to 15 mWcm⁻² (± 3%). The working area was covered with a blackout fabric (Thorlabs BK5). Fluorescence signals were directed to a 4-inch square first-surface silver mirror (Edmund Optics, 84,448) and then to a filter set (Thorlabs, 2 × FELH01000). At the end, the filtered signals were collected using an Allied Vision Goldeye G-032 Cool TEC2 camera with sensor set point at − 30 °C and equipped with a C-mount lens (Navitar, SWIR-35). The assembly was partially enclosed to avoid exposure to unwanted light. The images were acquired using platform independent Vimba SDK (Allied Vision) with a uniform acquisition time of 10 ms. During imaging mice were placed in supine position over pre-defined area under the influence of isoflurane. Inflammation in the tail was induced by intramuscular injection of histamine (0.02 mg/ml). MATLAB programming environment was used for processing and analysis of the acquired images.