Quantitative nmr microscopy of multicellular tumor spheroids and confrontation cultures

Brandl, Matthias; Tonn, Jörg‐Christian; Kotitschke, K.; Goldbrunner, Roland; Kerkau, Siglinde; Haase, Axel

doi:10.1002/mrm.1910340416

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…In order to characterise different cell and tissue types and to investigate changes in their structure or function, T 1 and T 2 maps are often employed in medical and biological MR imaging [1][2][3][4][5]. Especially in functional studies of plants, these parameters can offer insight into cell sizes, water exchange times through cell membranes, water activity and content, ion concentrations, nutritional state and vitality, etc.…”

Section: Introductionmentioning

confidence: 99%

Diffusion generated T1 and T2 contrast

Kaufmann

Seiberlich

Haase

et al. 2008

Journal of Magnetic Resonance

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Section: Introductionmentioning

confidence: 99%

Diffusion generated T1 and T2 contrast

Kaufmann

Seiberlich

Haase

et al. 2008

Journal of Magnetic Resonance

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“…Moreover, elevated ADC values have been correlated with the necrotic fraction of animal tumor models (6,24). In spheroids, mean diffusion coefficients are higher in the necrotic center than the periphery, which contains proliferating cells (25). In human breast cancer xenografts and radiation-induced fibrosarcomas, high ADC values are coincident with necrotic areas, which have low cellularity (17,26).…”

Section: Introductionmentioning

confidence: 99%

MRI‐measured water mobility increases in response to chemotherapy via multiple cell‐death mechanisms

et al. 2007

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Numerous pre-clinical and clinical reports have demonstrated that the MRI-measured apparent diffusion coefficient of water (ADC) increases early in the response to a wide variety of anti-cancer therapies. It has been proposed that this increase in ADC generally results from an increase in the tumor extracellular volume fraction leading to a greater degree of unrestricted water motion. Furthermore, an increase in extracellular volume has been ascribed to the cell shrinkage that occurs early in the process of programmed cell death. However, other modes of death can be initiated soon after beginning therapy. These other modes of death include mitotic catastrophe and necrosis, and may also involve changes in the fraction of water with unrestricted motion. This work examines whether MRI-measured ADC is altered in response to therapies that induce cell death via non-apoptotic mechanisms and correlates ADC changes with cell death modalities regionally within the tumor. Apoptotic responses were limited to the tumor periphery in apoptosis-proficient tumors. Apoptosis was not observed in deficient tumors. Mitotic catastrophe was observed after treatment at the periphery and deeper into the tumor. Necrosis was the predominant response in the center of the tumor. ADC changes were moderate in the periphery and larger in the center. The results indicate that early and significant changes in ADC can occur in concert with mitotic catastrophe and lytic necrosis in the absence of apoptosis. Hence, changes in ADC may be a generalized measure of cytotoxic response to chemotherapy.

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“…3,4 In spheroids, mean diffusion coefficients were lower (0.59 ± 0.12 µ 2 /ms) for proliferating cells, compared to necrotic centers (0.85 ± 0.14 µ 2 /ms). 5 Similarly, inverse correlations between ADC w values and pO 2 have been observed. 6 Higher ADC w values observed in necrotic areas were associated with low pO 2 values.…”

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confidence: 73%

Diffusion‐Weighted MRI and Response to Anti‐Cancer Therapies

Galons

Morse

Jennings

et al. 2003

Israel Journal of Chemistry

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In oncology practice, longitudinal studies are routinely conducted to monitor the size and enhancement of tumors in cancer patients undergoing therapy. Imaging protocols typically use gadolinium-enhanced T 1 -weighted images or T 2weighted images from which tumor size is inferred and tumor response estimated. The past few years have also seen the emergence of diffusion-weighted magnetic resonance imaging (DWMRI) as a potential alternative to monitor therapeutic response (Kauppinen, R.A., NMR Biomed. 2002, 15, 6). The attractiveness of DWMRI resides in its ability to detect local microstructural changes associated with treatment long before their effects are translated into effective size changes. Damage to cell membrane integrity, changes in viscosity, and/or relative size of intra-vs. extracellular compartments all translate into changes in the apparent diffusion coefficient of tumor water measured by DWMRI. This dependence makes DWMRI a particularly sensitive method to detect response to a wide variety of chemotherapeutic agents. This review will focus on the emerging role of DWMRI to monitor the response of tumors to anti-cancer chemotherapies.

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Quantitative nmr microscopy of multicellular tumor spheroids and confrontation cultures

Cited by 15 publications

References 15 publications

Diffusion generated T1 and T2 contrast

Diffusion generated T1 and T2 contrast

MRI‐measured water mobility increases in response to chemotherapy via multiple cell‐death mechanisms

Diffusion‐Weighted MRI and Response to Anti‐Cancer Therapies

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