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Nia, Hadi

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Nia

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Nia, Hadi
Author's Publications: search.filters.isAuthorOfPublication.66883097-6f03-4975-a1a4-5a19dc034fd3

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    Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium
    (Springer Science and Business Media LLC, 2019-01-07) Seano, Giorgio; Nia, Hadi; Emblem, Kyrre E.; Datta, Meenal; Ren, Jun; Krishnan, Shanmugarajan; Kloepper, Jonas; Pinho, Marco C.; Ho, William W.; Ghosh, Mitrajit; Askoxylakis, Vasileios; Ferraro, Gino B.; Riedemann, Lars; Gerstner, Elizabeth; Batchelor, Tracy; Wen, Patrick; Lin, Nancy; Grodzinsky, Alan J.; Fukumura, Dai; Huang, Peigen; Baish, James W.; Padera, Timothy; Munn, Lance; Jain, Rakesh
    The compression of brain tissue by a tumour mass is believed to be a major cause of the clinical symptoms seen in patients with brain cancer. However, the biological consequences of these physical stresses on brain tissue are unknown. Here, via imaging studies in patients and by using mouse models of human brain tumours, we show that a subgroup of primary and metastatic brain tumours, classified as nodular on the basis of their growth pattern, exert solid stress on the surrounding brain tissue, causing a decrease in local vascular perfusion as well as neuronal death and impaired function. We demonstrate a causal link between solid stress and neurological dysfunction by applying and removing cerebral compression, which respectively mimic the mechanics of tumour growth and of surgical resection. We also show that, in mice, treatment with lithium reduces solid-stress-induced neuronal death and improves motor coordination. Our findings indicate that brain-tumour-generated solid stress impairs neurological function in patients, and that lithium as a therapeutic intervention could counter these effects.
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    Laser Speckle Rheology for evaluating the viscoelastic properties of hydrogel scaffolds
    (Nature Publishing Group, 2016) Hajjarian, Zeinab; Nia, Hadi; Ahn, Shawn; Grodzinsky, Alan J.; Jain, Rakesh; Nadkarni, Seemantini
    Natural and synthetic hydrogel scaffolds exhibit distinct viscoelastic properties at various length scales and deformation rates. Laser Speckle Rheology (LSR) offers a novel, non-contact optical approach for evaluating the frequency-dependent viscoelastic properties of hydrogels. In LSR, a coherent laser beam illuminates the specimen and a high-speed camera acquires the time-varying speckle images. Cross-correlation analysis of frames returns the speckle intensity autocorrelation function, g2(t), from which the frequency-dependent viscoelastic modulus, G*(ω), is deduced. Here, we establish the capability of LSR for evaluating the viscoelastic properties of hydrogels over a large range of moduli, using conventional mechanical rheometry and atomic force microscopy (AFM)-based indentation as reference-standards. Results demonstrate a strong correlation between |G*(ω)| values measured by LSR and mechanical rheometry (r = 0.95, p < 10−9), and z-test analysis reports that moduli values measured by the two methods are identical (p > 0.08) over a large range (47 Pa – 36 kPa). In addition, |G*(ω)| values measured by LSR correlate well with indentation moduli, E, reported by AFM (r = 0.92, p < 10−7). Further, spatially-resolved moduli measurements in micro-patterned substrates demonstrate that LSR combines the strengths of conventional rheology and micro-indentation in assessing hydrogel viscoelastic properties at multiple frequencies and small length-scales.
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    Publication
    Solid stress and elastic energy as measures of tumour mechanopathology
    (Springer Nature, 2016) Nia, Hadi; Jain, Rakesh; Liu, Hao; Seano, Giorgio; Datta, Meenal; Jones, Dennis; Rahbari, Nuh; Incio, Joao; Chauhan, Vikash; Jung, Keehoon; Martin, John D.; Askoxylakis, Vasileios; Padera, Timothy; Fukumura, Dai; Boucher, Yves; Hornicek, Francis; Grodzinsky, Alan J; Baish, James W; Munn, Lance
    Solid stress and tissue stiffness affect tumour growth, invasion, metastasis and treatment. Unlike stiffness, which can be precisely mapped in tumours, the measurement of solid stresses is challenging. Here, we show that two-dimensional spatial mappings of solid stress and the resulting elastic energy in excised or in situ tumours with arbitrary shapes and wide size ranges can be obtained via three distinct and quantitative techniques that rely on the measurement of tissue displacement after disruption of the confining structures. Application of these methods in models of primary tumours and metastasis revealed that: (i) solid stress depends on both cancer cells and their microenvironment; (ii) solid stress increases with tumour size; and (iii) mechanical confinement by the surrounding tissue significantly contributes to intratumoural solid stress. Further study of the genesis and consequences of solid stress, facilitated by the engineering principles presented here, may lead to significant discoveries and new therapies.