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Art for Mental Health

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Caleb Campbell
Caleb Campbell

50 Shades Of Gray Test.mov =LINK=


The movie adaptation of Fifty Shades Darker is scheduled to hit theaters on Feb. 10, continuing the risque storyline of the bestselling novel Fifty Shades of Grey series. Which got us wondering: Is it actually possible for a person to distinguish that many shades of such a neutral color?




50 shades of gray test.mov



What was Anastasia's major? How did Christian like to exercise? What was the name of his helicopter? From 514 pages and over two hours of film, can you remember all the shades or will you be left heartbroken before the sequel?


Cellular organization of brain tissue. In white matter (corona radiata), myelinated axons allow for rapid nerve impulse conduction; intermediate oligodendrocytes connect and form several myelin sheaths. Fibrous astrocytes ensure supply of nutrients and synaptic processing. In gray matter (cortex), neurons form synapses with each other and with protoplasmic astrocytes. In both white and gray matter, microglial cells contribute to clearance of debris and synapse remodeling. Reprinted from [27] under Creative Commons Attribution License (CC BY)


Figure 5 illustrates the major cell types in white and gray matter tissue. Gray matter regions contain mainly neuronal cell bodies, protoplasmic astrocytes providing neurons with nutrients, and microglia as active immune defense. White matter regions, on the contrary, contain axons, oligodendrocytes which wrap isolating myelin sheath around the axons, fibrous astrocytes, and microglia [27]. Notably, not only the cellular composition may be relevant for macroscopic tissue mechanics but also extracellular matrix components. The latter may show regional trends that even differ from those of brain cells.


Figure 10 shows stress relaxation experiments for all four brain regions [22], which confirm the extreme time-dependence of brain tissue with a stress relaxation of up to 80% within only 300 s. Interestingly, white matter tissue, with a stress relaxation of more than 70% after 300 s, is more viscous and responds more slowly than gray matter, with a stress relaxation of approximately 65%. Within white matter, specimens from the corpus callosum relax faster than specimens from the corona radiata. Within gray matter, the basal ganglia and the cortex exhibit a similar relaxation behavior. Stress relaxation percentages are slightly higher in shear than in compression, but both loading modes show similar regional dependencies.


Figures 11 and 12 illustrate that brain tissue not only stiffens with increasing strain but also with increasing strain rate. Rate-dependence of brain stiffness has consistently been reported in the literature using different testing techniques: shear testing or oscillatory shear testing [44, 127, 151], uniaxial compression or tension [57, 83, 85, 132, 137, 140], indentation [20, 107, 136, 163], and magnetic resonance elastography [36, 145]. Figure 11 illustrates uniaxial compression, tension, and simple shear experiments performed at strain rates of 0.33 and 0.0067 1/s, respectively. Figure 12 shows nanoindentation experiments over a loading rate spectrum from 1 to \(160\,\mu \hbox m/s\). Within the analyzed loading rate regime both gray and white matter double their maximum forces and corresponding moduli when increasing the loading rate by two orders of magnitude [20]. This effect becomes particularly important for applications such as blunt or traumatic brain injury, where even higher strain rates occur [137, 158].


Our results in Fig. 11 suggest that the effect of strain rate is more pronounced in white matter regions than in gray matter regions. This observation agrees well with the stress relaxation experiments in Fig. 10, which show that white matter relaxes faster than gray matter. A possible explanation for this behavior could be the difference in the permeability of gray and white matter. While for slower loadings, fluid has more time to escape, for faster loadings, it offers resistance, which leads to higher stresses. As white matter specimens seem to loose a higher amount of fluid during unconfined experiments than gray matter specimens [22, 23, 25], their strain rate effect is more pronounced.


Loading rate sensitivity of gray and white matter. Sensitivity of indentation force versus indentation depth for varying loading rates reveals the rate-dependent nature of brain tissue. Indentation force and modulus increase with increasing loading rate. Adapted from [20]


Our results agree well with an early study on the rheological shear response of human brain tissue [151], which showed higher directional variation in gray matter than in white matter, but neither of the differences appeared significant. Contradictory to our findings, studies on porcine brain tissue found a significantly stiffer shear response orthogonal to nerve fibers than along fibers in the corpus callosum [134]. In the corona radiata, however, the trend was opposite. The authors of this study sheared each specimen in two orthogonal directions similar to our experiments, but only estimated fiber orientations from anatomical knowledge and used rectangular specimen dimensions of \(10\times 5\times 1\) mm\(^3\). Notably, the measured shear stresses were consistently higher in the direction of the longer axis corresponding to the direction orthogonal to fibers in the corpus callosum, and to the fiber direction in the corona radiata. This could indicate that directional dependencies are an artifact of the non-cuboidal specimen dimensions rather than a result of the anisotropic distribution of nerve fibers, which could explain the contradictory results. Interestingly, yet other studies on the porcine corpus callosum found opposite trends with a significantly stiffer response in the fiber direction than perpendicular to it in dynamic shear [53] and tensile tests [165]. In both studies, specimens were relatively large with dimensions of up to \(16\times 16\times 3\,\hbox mm^3\) and \(5\times 5\times 60\,\hbox mm^3\). Our diffusion tensor images showed that even in the much larger human brain, it would be challenging to extract specimens of that size that exhibit a sufficiently uniform microstructure. We therefore interpret the corresponding results with a degree of caution.


Due to its high microstructural heterogeneity, brain tissue can hardly be considered as a single material with unified material properties. While early studies on the mechanical properties of the brain focused on brain tissue as a whole, more recent experimental studies have distinguished between different regions, i.e., white and gray matter [20, 57, 114, 163], or, even more refined, cortex, basal ganglia, corona radiata and corpus callosum, as depicted in Fig. 4 [22, 85]. Others tested the individual properties of the cerebrum, cerebellum, pons, and medulla [109].


Regional variation of gray and white matter moduli. Measurements at three different slices and three different locations reveal that the specimen moduli vary markedly across the brain. Gray matter, left, is softer than white matter, right, and displays smaller regional variations. Black horizontal lines indicate the mean; gray zones indicate the standard deviation. Adapted from [20]


Firstly, the rheological difference discussed in Sect. 3.4 leads to a rate-dependency of regional trends: White matter stiffens relative to gray matter with increasing loading rate. As a result, shear, compression or tension experiments in the fast loading regime associated with phenomena on the order of seconds or milliseconds such as traumatic brain injury have reported a higher stiffness for white matter from the corona radiata than for cortical gray matter [85, 114], while experiments in the slow loading regime, as those shown in Fig. 11, indicate the reversed relationship. The strain-rate dependence of regional trends is also supported by a recent study showing that inter-regional mechanical properties become increasingly heterogeneous with increasing strain rate [108].


When comparing the porous nature of different brain regions, our experiments indicate that the largest amount of fluid escapes from white matter specimens of the corpus callosum, closely followed by the corona radiata, while gray matter specimens from the cortex loose the least amount of fluid [23]. This difference in the permeability of gray and white matter is also reflected in larger hysteresis areas in white matter than in gray matter during cyclic loading [22]. We can rationalize these observations with the underlying tissue microstructure: the corpus callosum consists of a sparsely cross-linked network of unidirectional fibers, whereas the cortex consists of a densely connected network of dendrites that traps the fluid phase inside the tissue.


In summary, because of its ultrasoft nature, brain tissue stiffness recordings are highly sensitive to the fluid content of the sample. Undrained samples are stiffer than drained samples, and drainage rates depend critically on the tissue microstructure. These effects are less pronounced in other types of tissues with a lower fluid volume fraction. This explains why the reported stiffness values of brain tissue vary hugely. Without an explicit mention of loading rates, drainage conditions, and sample size and geometry, it is virtually impossible to compare stiffness values recorded under different test conditions. The concept of a single one gray or white matter stiffness value simply does not exist for brain tissue, and it is critical for computational simulations to understand exactly which situation applies to select the appropriate model and parameter values.


Figure 6 summarizes various testing techniques to probe the mechanical behavior of brain tissue at different spatial and temporal scales. A prominent method to probe brain tissue at small spatial scales is atomic force microscopy [35]. Unlike nanoindentation on the meso-scale with relatively large indenter tips shown in Fig. 18, atomic force microscopy has resulted in yet higher stiffness in gray than in white matter [94]. In atomic force microscopy, the size of the indenter tip is on the order of the dimensions of individual cells. The indenter seems to be small enough not to trap the fluid beneath the tip which suggests that these tests probe the solid component of brain tissue similar to unconfined experiments at slow loading rates. 041b061a72


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