Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo

Zhao, Ming; Pipe, James G.; Bonnett, John; Evelhoch, Jeffrey L.

doi:10.1038/bjc.1996.11

Cited by 173 publications

(133 citation statements)

References 20 publications

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“…Optically detected changes in ctH 2 O may represent subtle variations in tumor cell density and edema, where reductions in tumor water imply diminished cellularity due to cell death (52). Recent studies in murine tumor models support this concept and suggest that changes in the ADC w reflect tumor therapeutic response (53).…”

Section: Discussionmentioning

confidence: 69%

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Cerussi

Hsiang

Shah

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

276

259

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Diffuse optical spectroscopy (DOS) and imaging are emerging diagnostic techniques that quantitatively measure the concentration of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctO 2Hb), water (ctH 2O), and lipid in cm-thick tissues. In early-stage clinical studies, diffuse optical imaging and DOS have been used to characterize breast tumor biochemical composition and monitor therapeutic response in stage II/III neoadjuvant chemotherapy patients. We investigated whether DOS measurements obtained before and 1 week into a 3-month adriamycin/cytoxan neoadjuvant chemotherapy regimen can predict final, postsurgical pathological response. Baseline DOS measurements of 11 patients before therapy revealed significant increases in tumor ctHHb, ctO 2Hb, ctH 2O, and spectral scattering slope, and decreases in bulk lipids, relative to normal breast tissue. Tumor concentrations of ctHHb, ctO 2Hb, and ctH2O dropped 27 ؎ 15%, 33 ؎ 7%, and 11 ؎ 15%, respectively, within 1 week (6.5 ؎ 1.4 days) of the first treatment for pathology-confirmed responders (n ‫؍‬ 6), whereas nonresponders (n ‫؍‬ 5) and normal side controls showed no significant changes in these parameters. The best single predictor of therapeutic response 1 week posttreatment was ctHHb (83% sensitivity, 100% specificity), while discrimination analysis based on combined ctHHb and ctH 2O changes classified responders vs. nonresponders with 100% sensitivity and specificity. In addition, the pretreatment tumor-to-normal ctO 2Hb ratio was significantly higher in responders (2.82 ؎ 0.44) vs. nonresponders (1.82 ؎ 0.49). These results highlight DOS sensitivity to tumor cellular metabolism and biochemical composition and demonstrate its potential for predicting and monitoring an individual's response to treatment.diffuse optical imaging ͉ frequency-domain photon migration ͉ near-infrared ͉ tissue spectroscopy ͉ translational research O ptimal management locally advanced breast cancer (LABC) remains a complex therapeutic problem (1). LABC represents 5-20% of all newly diagnosed breast cancers in the United States with a higher incidence in medically underserved areas (2). Treatment for LABC has evolved from radical mastectomy to preoperative neoadjuvant chemotherapy followed by mastectomy or breast conservation therapy (3). Despite aggressive local therapy, long-term patient survival is still poor. LABC remains controversial because of uncertainties in determining the optimal intensity and duration of neoadjuvant chemotherapy and evaluating therapeutic response (2, 4, 5).Neoadjuvant chemotherapy response is determined by serial physical examination, mammography and/or ultrasound. Complete pathological response (cPR) is an important therapeutic endpoint that is a surrogate for eradicating micrometastases, and strongly correlates with patient survival (6). Thus one goal of neoadjuvant chemotherapy monitoring is to determine early when a patient will demonstrate cPR. Many studies revealed significant discrepancies between clinical response assessments and final pathology (7-9).A rece...

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Section: Discussionmentioning

confidence: 69%

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Cerussi

Hsiang

Shah

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

276

259

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“…An increase in water ADC after effective chemotherapy has been demonstrated in glioma (Ross et al, 2003;Hall et al, 2004), fibrosarcoma (Zhao et al, 1996), and human breast carcinoma (Galons et al, 1999). By contrast, no significant changes in water ADC were observed in a human breast carcinoma xenograft model after tumor necrosis factor-related apoptosis-inducing ligand therapy despite significant tumor growth delay (Chinnaiyan et al, 2000).…”

Section: Discussionmentioning

confidence: 89%

Early changes in apparent diffusion coefficient as an indicator of response to sorafenib in hepatocellular carcinoma

Zhao

Guo

Yang

et al. 2014

J. Zhejiang Univ. Sci. B

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Objective: The relationship between apparent diffusion coefficient (ADC) and chemotherapy has been established. However, whether ADC could be considered as a measure for monitoring response to sorafenib in hepatocellular carcinoma (HCC) has not been demonstrated. This study was to investigate the ADC changes of advanced HCC under sorafenib treatment. Methods: Athymic mice with HepG2 xenografts were allocated to two groups: control and sorafenib (40 mg/kg, bid). T2 and diffusion images were acquired at each time point (0, 10, 14, and 18 d post-therapy). Tumor volume and changes in ADC were calculated. Results: Tumor volumes on Days 10, 14, and 18 after treatment showed significant decreases in the sorafenib-treated group compared with the control. Pretreatment ADC values were not significantly different between the control and treated groups. A slow increase in ADC in the peripheral zone of tumors appeared in the treated group, which was significantly higher compared with the control group on Days 10, 14, and 18. In the central part of tumors on Day 10 after treatment, an increase in ADC appeared in the treated and control groups, the ADC of the control group being significantly lower compared with the treated tumors. From Day 10 to Day 14, the ADC map showed a progressive decrease in the central region of tumors in the treated and control groups. However, this change is more significant in the treated groups. Conclusions: Early changes in mean ADC correlated with sorafenib treatment in HCC, which are promising indicators for predicting sorafenib response in this carcinoma.

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“…Diffusion-weighted MRI can be used to detect changes in the apparent diffusion coefficient (ADC) for tissue water associated with changes in tissue and intracellular structure (Zhao et al, 1996;Gallons et al, 1999;Ross et al, 2003;Moffat et al, 2005). Proton magnetic resonance spectroscopy (MRS) can be used to characterise breast lesions through differences in the ratio of fat and water signals (Chu et al, 1987;Sijens et al, 1988) or the intensity of signal from choline-containing compounds (Bradamante et al, 1988;Katz-Brull et al, 2002;Bolan et al, 2003;Jacobs et al, 2004;Jacobs et al, 2005).…”

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confidence: 99%

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy

et al. 2006

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A prospective study was undertaken in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer in order to determine the ability of quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to predict ultimate tumour response (percentage decrease in volume) or to detect early response. Magnetic resonance imaging and MRS were carried out before treatment and after the second of six treatment cycles. Pharmacokinetic parameters were derived from T 1 -weighted dynamic contrast-enhanced MRI, water apparent diffusion coefficient (ADC) was measured, and tissue water : fat peak area ratios and water T 2 were measured using unsuppressed one-dimensional proton spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and ADC did not detect early response; however, early changes in water : fat ratios and water T 2 (after cycle two) demonstrated substantial prognostic efficacy. Larger decreases in water T 2 accurately predicted final volume response in 69% of cases (11/16) while maintaining 100% specificity and positive predictive value. Small/absent decreases in water : fat ratios accurately predicted final volume non-response in 50% of cases (3/6) while maintaining 100% sensitivity and negative predictive value. This level of accuracy might permit clinical application where early, accurate prediction of non-response would permit an early change to second-line treatment, thus sparing patients unnecessary toxicity, psychological morbidity and delay of initiation of effective treatment.

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Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo

Cited by 173 publications

References 20 publications

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy

Early changes in apparent diffusion coefficient as an indicator of response to sorafenib in hepatocellular carcinoma

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy

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