Diffuse Optical Spectroscopic Imaging Measurements Research Articles

In vivo, noninvasive functional measurements of bone sarcoma using diffuse optical spectroscopic imaging.

Diffuse optical spectroscopic imaging (DOSI) is an emerging near-infrared imaging technique that noninvasively measures quantitative functional information in thick tissue. This study aimed to assess the feasibility of using DOSI to measure optical contrast from bone sarcomas. These tumors are rare and pose technical and practical challenges for DOSI measurements due to the varied anatomic locations and tissue depths of presentation. Six subjects were enrolled in the study. One subject was unable to be measured due to tissue contact sensitivity. For the five remaining subjects, the signal-to-noise ratio, imaging depth, optical properties, and quantitative tissue concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipids from tumor and contralateral normal tissues were assessed. Statistical differences between tumor and contralateral normal tissue were found in chromophore concentrations and optical properties for four subjects. Low signal-to-noise was encountered during several subject's measurements, suggesting increased detector sensitivity will help to optimize DOSI for this patient population going forward. This study demonstrates that DOSI is capable of measuring optical properties and obtaining functional information in bone sarcomas. In the future, DOSI may provide a means to stratify treatment groups and monitor chemotherapy response for this disease.

Noninvasive optical imaging of resistance training adaptations in human muscle.

.A quantitative and dynamic analysis of skeletal muscle structure and function can guide training protocols and optimize interventions for rehabilitation and disease. While technologies exist to measure body composition, techniques are still needed for quantitative, long-term functional imaging of muscle at the bedside. We evaluate whether diffuse optical spectroscopic imaging (DOSI) can be used for long-term assessment of resistance training (RT). DOSI measures of tissue composition were obtained from 12 adults before and after 5 weeks of training and compared to lean mass fraction (LMF) from dual-energy X-ray absorptiometry (DXA). Significant correlations were detected between DXA LMF and DOSI-measured oxy-hemo/myoglobin, deoxy-hemo/myoglobin, total-hemo/myoglobin, water, and lipid. RT-induced increases of in oxy-hemo/myoglobin (, ) and total-hemo/myoglobin (, ) from the medial gastrocnemius were detected with DOSI and accompanied by increases in lean soft tissue mass (, ) and increases in 1 rep-max strength (, ). DOSI measures of vascular and/or muscle changes combined with correlations between DOSI and DXA suggest that quantitative diffuse optical methods can be used to evaluate body composition, provide feedback on long-term interventions, and generate new insight into training-induced muscle adaptations.

Diffuse optical spectroscopic imaging of subcutaneous adipose tissue metabolic changes during weight loss.

BackgroundChanges in subcutaneous adipose tissue (AT) structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. Measurements of AT physiology could provide new insight into metabolic disease progression and response to therapy. An emerging functional imaging technology, Diffuse Optical Spectroscopic Imaging (DOSI), was used to obtain quantitative measures of near infrared (NIR) AT optical and physiological properties.Methods10 overweight or obese adults were assessed during three-months on calorie-restricted diets. DOSI-derived tissue concentrations of hemoglobin, water, and lipid and the wavelength-dependent scattering amplitude (A) and slope (b) obtained from 30 abdominal locations and three time points (T0, T6, T12) were calculated and analyzed using linear mixed effects models, and were also used to form 3D surface images.ResultsSubjects lost a mean of 11.7 ± 3.4% of starting weight, while significant changes in A (+0.23 ± 0.04 mm−1, adj. p < 0.001), b (−0.17 ± 0.04, adj. p < 0.001), tissue water fraction (+7.2 ± 1.1%, adj. p < 0.001) and deoxyhemoglobin [HbR] (1.1 ± 0.3 µM, adj. p < 0.001) were observed using mixed effect model analysis.DiscussionOptical scattering signals reveal alterations in tissue structure which possibly correlate with reductions in adipose cell volume, while water and hemoglobin dynamics suggest improved AT perfusion and oxygen extraction. These results suggest that DOSI measurements of NIR optical and physiological properties could be used to enhance understanding of the role of AT in metabolic disorders and provide new strategies for diagnostic monitoring of obesity and weight loss.

Abstract S4-04: Predicting pre-surgical neoadjuvant chemotherapy response in breast cancer using diffuse optical spectroscopic imaging (DOSI): Results from the ACRIN 6691 study

Abstract Background: DOSI is an experimental imaging technique that employs risk-free near-infrared light for quantitative measurements of breast tissue perfusion, metabolism, and composition without exogenous contrast. A multi-center ACRIN 6691 study was designed to evaluate whether changes from baseline to mid-therapy in a DOSI-derived Tissue Optical Index (TOI) could predict pathologic complete response (pCR) in breast cancer neoadjuvant chemotherapy (NAC). Methods: DOSI instruments were constructed at the University of California, Irvine and delivered to 6 participating sites. Bedside measurements were conducted by scanning a handheld probe over a region of interest (up to ∼10 x 10 cm2) on both breasts. Instruments were standardized and validated using a common set of tissue simulating phantoms and protocols. DOSI-derived near-infrared absorption and scattering spectra (650-1000 nm) were used to calculate the tissue concentration of oxy- and deoxyhemoglobin (ctO2Hb, ctHHb), water (ctH2O), %lipid and the tissue optical index (TOI=ctHHb x ctH2O/%lipid) in each probe location. Baseline to mid-therapy changes in the tumor to normal (T/N) TOI ratio were evaluated from DOSI images as the primary imaging endpoint for predicting clinical outcome (pCR). 60 female breast cancer patients (ages 28-69 years, mean 48.9±11), with locally advanced disease (tumors &amp;gt;2cm) were enrolled across the 6 institutions. DOSI measurements were performed at baseline, during the first week of therapy, at midpoint, and at the completion of NAC. Logistic regression was used to assess the association between pathologic complete response (pCR) and % change in T/N TOI from baseline to mid-therapy. In addition, area under the receiver operating characteristic curve (ROC AUC) and its corresponding 95% confidence interval were calculated. Results: Of the 34 participants (mean age 48.4 ± 10.7) with complete and evaluable data, 10 (29%) achieved pCR as determined by central pathology review. The % change in TOI ratio ranged from -82% to 321%, with a median of -36%. Using -40% as a threshold, we found that subjects in the group with a 40% or more decrease in T/N TOI were more likely to be pCR (p=0.0586, OR=4.667, 95% CI: 0.945 to 23.038). The % change in TOI ratio from baseline to mid-therapy has an AUC of 0.604 (95% CI: 0.394 to 0.814) to distinguish pCR from non-pCR. Conclusions: DOSI has been successfully implemented in a multi-center setting and changes in T/N TOI are a promising predictor of NAC clinical outcome (pCR). A larger study population is needed to fully assess the utility of TOI and other DOSI imaging endpoints for guiding therapies and predicting NAC response in individual subjects. ACRIN receives funding from the NCI through U01 CA079778 and U01 CA080098. Citation Format: Bruce J Tromberg, Zheng Zhang, Anais Leproux, Thomas D O'Sullivan, Albert E Cerussi, Philip Carpenter, Rita Mehta, Darren Roblyer, Wei Yang, Keith D Paulsen, Brian W Pogue, Shudong Jiang, Peter Kaufman, Arjun G Yodh, So-Hyun Chung, Mitchell Schnall, Brad Snyder, Nola Hylton, David A Boas, Stefan A Carp, Steven J Isakoff, David Mankoff. Predicting pre-surgical neoadjuvant chemotherapy response in breast cancer using diffuse optical spectroscopic imaging (DOSI): Results from the ACRIN 6691 study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S4-04.

Abstract P4-01-12: Optical imaging of breast density correlates with magnetic resonance imaging in patients undergoing neoadjuvant chemotherapy

Abstract Background: In addition to being a strong risk factor for breast cancer, data from recent studies suggests that breast density changes correlate with response to preventative or adjuvant tamoxifen treatment for breast cancer. Breast density may be a surrogate biomarker for survival and indication of the need for additional treatments such as radiotherapy. However, quantitative methods to assess breast density in the clinic are limited. In this study, we assess how Diffuse Optical Spectroscopic Imaging (DOSI) may be used to evaluate and understand changes in breast density in patients undergoing neoadjuvant chemotherapy. Methods: DOSI was used to measure hemodynamic and metabolic information from the contralateral normal breast of 28 breast cancer patients undergoing neoadjuvant chemotherapy. DOSI uses near-infrared light to determine absolute tissue molar concentrations of oxyhemoglobin (ctO2Hb), deoxyhemoglobin (ctHHb), water, and lipid content without requirement of an exogenous contrast agent. DOSI measurements were compared to 3.0T MRI measured fibroglandular density before and during therapy. Results: Water (r = 0.843; P&amp;lt;0.001), ctHHb (r = 0.785; P = 0.003), and lipid (r = -0.707; P = 0.010) concentration measured with DOSI correlated strongly with MRI-measured density before therapy. During neoadjuvant treatment measured at ∼90 days after treatment commenced, significant reductions were observed in ctO2Hb for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration for premenopausal subjects (- 1.9%; 95% CI, -17.1 to -6.7) compared to baseline. Lipid content increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5) and water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6). Percentage change in water at the end of therapy compared with baseline correlated strongly with percentage change in MRI-measured density (r = 0.864; P = 0.012). Discussion: For this patient cohort, non-invasive optical measurement may provide an assessment of breast density and yield additional information that complements MRI and mammography techniques. We demonstrate a strong baseline correlation between water and ctHHb with breast density, reflecting the increased water content and rate of metabolism in fibroglandular breast tissue. Significant changes in optical markers for vascular density and supply (ctO2Hb and water) are observed during treatment. A significant decrease in ctO2Hb is observed in both menopausal groups. The steady reduction of ctO2Hb without a corresponding decrease in ctHHb suggests that chemotherapy agents act directly on the normal breast tissue, perhaps by causing a reduction of perfusion. The greater reduction in breast-tissue water in premenopausal subjects suggests that chemo-reduced ovarian hormone levels may exert a role in reducing breast-tissue density. Although from a limited patient dataset, these results suggest that DOSI may provide new functional indices of breast density based on hemoglobin and water that could be used at the bedside to assess response to therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-12.

Assessing tumor contrast in radiographically dense breast tissue using Diffuse Optical Spectroscopic Imaging (DOSI)

IntroductionRadiographic density adversely affects the performance of X-ray mammography and can be particularly problematic in younger and high-risk women. Because of this limitation, there is significant ongoing effort to develop alternative cancer screening and detection strategies for this population. This pilot study evaluates the potential of Diffuse Optical Spectroscopic Imaging (DOSI) to image known tumors in dense breast tissue.MethodsWe performed a retrospective analysis on 24 radiographically dense breast cancer subjects measured with DOSI over a four-year period (Breast Imaging Reporting and Data System - BI-RADS, category 3 and 4, average age = 39 ± 7.6, average maximum size 31 ± 17 mm). Two previously-described DOSI contrast functions, the tissue optical index (TOI) and the specific tumor component (STC), which are based upon the concentrations and spectral signatures of hemoglobin, water and lipids, respectively, were used to form 2D optical images of breast tumors.ResultsUsing TOI and STC, 21 out of 24 breast tumors were found to be statistically different from the surrounding highly vascularized dense tissue and to be distinguishable from the areolar region. For these patients, the tumor to normal contrast was 2.6 ± 1.2 (range 1.3 to 5.5) and 10.0 ± 7.5 (range 3.3 to 26.4) for TOI and STC, respectively. STC images were particularly useful in eliminating metabolic background from the retroareolar region which led to identification of two out of four retroareolar tumors.ConclusionsUsing both the abundance and the disposition of the tissue chromophores recovered from the DOSI measurements, we were able to observe tumor contrast relative to dense breast tissue. These preliminary results suggest that DOSI spectral characterization strategies may provide new information content that could help imaging breast tumors in radiographically dense tissue and in particular in the areolar complex.

Optical imaging correlates with magnetic resonance imaging breast density and revealscomposition changes during neoadjuvant chemotherapy

IntroductionIn addition to being a risk factor for breast cancer, breast density has been hypothesized to be a surrogate biomarker for predicting response to endocrine-based chemotherapies. The purpose of this study was to evaluate whether a noninvasive bedside scanner based on diffuse optical spectroscopic imaging (DOSI) provides quantitative metrics to measure and track changes in breast tissue composition and density. To access a broad range of densities in a limited patient population, we performed optical measurements on the contralateral normal breast of patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSI parameters, including tissue hemoglobin, water, and lipid concentrations, were obtained and correlated with magnetic resonance imaging (MRI)-measured fibroglandular tissue density. We evaluated how DOSI could be used to assess breast density while gaining new insight into the impact of chemotherapy on breast tissue.MethodsThis was a retrospective study of 28 volunteers undergoing NAC treatment for breast cancer. Both 3.0-T MRI and broadband DOSI (650 to 1,000 nm) were obtained from the contralateral normal breast before and during NAC. Longitudinal DOSI measurements were used to calculate breast tissue concentrations of oxygenated and deoxygenated hemoglobin, water, and lipid. These values were compared with MRI-measured fibroglandular density before and during therapy.ResultsWater (r = 0.843; P < 0.001), deoxyhemoglobin (r = 0.785; P = 0.003), and lipid (r = -0.707; P = 0.010) concentration measured with DOSI correlated strongly with MRI-measured density before therapy. Mean DOSI parameters differed significantly between pre- and postmenopausal subjects at baseline (water, P < 0.001; deoxyhemoglobin, P = 0.024; lipid, P = 0.006). During NAC treatment measured at about 90 days, significant reductions were observed in oxyhemoglobin for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) and postmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentration for premenopausal subjects (-11.9%; 95% CI, -17.1 to -6.7) compared with baseline. Lipid increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5), and water increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6). Percentage change in water at the end of therapy compared with baseline correlated strongly with percentage change in MRI-measured density (r = 0.864; P = 0.012).ConclusionsDOSI functional measurements correlate with MRI fibroglandular density, both before therapy and during NAC. Although from a limited patient dataset, these results suggest that DOSI may provide new functional indices of density based on hemoglobin and water that could be used at the bedside to assess response to therapy and evaluate disease risk.

Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy

Diffuse optical spectroscopic imaging (DOSI) non-invasively and quantitatively measures tissue haemoglobin, water and lipid. Pilot studies in small groups of patients demonstrate that DOSI may be useful for longitudinal monitoring and predicting breast cancer neoadjuvant chemotherapy pathological response. This study evaluates the performance of a bedside DOSI platform in 34 breast cancer patients followed for several months. DOSI optical endpoints obtained at multiple timepoints are compared with final pathological response. Thirty-six stage II/III breast cancers (34 patients) were measured in vivo with DOSI prior to, in the middle of and after the completion of pre-surgical neoadjuvant chemotherapy. Cancer therapies ranged from standard anthracyclines to targeted therapies. Changes in DOSI-measured parameters at each timepoint were compared against final surgical pathology. Absolute changes in the tumour-to-normal (T/N) ratio of tissue deoxyhaemoglobin concentration (ctHHb) and relative changes in the T/N ratio of a tissue optical index (TOI) were most sensitive and correlate to pathological response. Changes in ctHHb and TOI were significantly different between tumours that achieved pathological complete response (pCR) versus non-pCR. By therapy midpoint, mean TOI-T/N changes were 47±8 versus 20±5 per cent for pCR versus non-pCR subjects, respectively (Z=0.011). Changes in ctHHb and TOI scaled significantly with the degree of pathological response (non-, partial and complete). DOSI measurements of TOI separated pCR from non-pCR by therapy midpoint regardless of drug or dosing strategy. This approach is well suited to monitoring breast tumour response and may provide feedback for optimizing therapeutic outcomes and minimizing side-effects.

Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment

Approximately 8-20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

Non-Invasive Measurement of Pathological Heterogeneity of Cancer Tissues Using Water State Information from Diffuse Optical Spectroscopic Imaging.

Abstract Background: In our previous work, we have shown that biochemical tissue water state correlates with histopathological scores of breast cancer (R=-0.96). Based on the result, we extended our research to test whether the tissue water measurement can differentiate heterogeneous pathological structures of cancer tissues of different grades. Diffuse Optical Spectroscopic Imaging (DOSI) measures water molecular vibrational states associated with macro-molecular complexes in tissues such as proteins in a non-invasive way without compression of the breast. For DOSI measurements, a large region over breast tumors is scanned using a hand-held probe and spectral information on each point is spatially mapped to generate an image.Subjects and Methods: DOSI was employed to measure 19 primary cancers (18 IDC and 1 ILC). The spectral features of tissue water absorption from 935 nm to 998nm were compared to those of a pure water spectrum measured at body temperature in order to acquire the Bound Water Index (BWI: the residual between tissue and pure water spectra). In the spectroscopic images, the average and standard deviation of the pixels less than 20% of the range of the BWI in the image were calculated based on our previous finding that carcinoma tissues have lower BWI (more free water). The same parameters were calculated on normal tissues from the same patients in order to compare the tissue heterogeneity. The standard deviation was divided by the average value of each tissue type, and this value is communicated as a Heterogeneity Index (HI).Results: In our in vivo clinical studies, the cancer tissues showed 51% higher heterogeneity than the normal tissues (cancer HI: 0.046±0.018, normal HI: 0.024±0.018, p&amp;lt;0.001). Furthermore, the low (N=4), medium (N=9) and high grade (N=6) tumors, defined by the Nottingham Bloom-Richardson histopathological scores (3-5: low, 6-7: med and 8-9: high), demonstrated increasing heterogeneity in the water disposition with the tumor grade. The medium and high grade tumors had 10.5 and 28% more heterogeneity than the low grade tumors in average (low grade HI: 0.041±0.015, med: 0.045±0.02 and high: 0.052±0.017).Discussion: The tissue water measurement using DOSI showed its ability to measure increased pathological heterogeneity in more invasive cancer tissues. This result supports our earlier finding that the BWI can report on histopathological grades of cancer tissues. These pathological properties were acquired in a completely non-invasive way with non-ionizing low power light. The results of this study suggest that the water state measurement using DOSI may be used as a non-invasive optical biopsy with high specificity. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5008.

Diffuse optical spectroscopic imaging measures tumor functional response to bevacizumab: initial studies.

Abstract Abstract #6056 Background: Diffuse Optical Spectroscopic Imaging (DOSI) is a non-invasive, bedside functional imaging technique that quantifies the concentrations and molecular states of tissue hemoglobin, water, and lipids. Pilot studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentrations before and after therapy. DOSI may offer a point-of-care measurement of tumor responses to therapeutic intervention. The majority of these DOSI studies have measured responses to Anthracyclines. However, the optical response to Bevacizumab has not been demonstrated in vivo in human subjects.&amp;#x2028; Materials and Methods: Twenty-one patients diagnosed with stage II/III cancers were followed with DOSI prior to and during their two-stage neoadjuvant chemotherapy regimen that featured (a) Anthracyclines (2-4 cycles) and (b) Trastuzumab/Bevacizumab (for HER2+/HER2- status, respectively). Changes between pre-treatment and pre-surgical DOSI-measured parameters were compared against final surgical pathology (complete, partial, or non-responder). A functional tissue optical index (TOI) was calculated that has been shown to discriminate between normal and malignant tissues.&amp;#x2028; Results: Both short-term and long-term changes in tumor physiology were observed. For both therapy strategies (N=21), statistically significant changes were measured in TOI from baseline to pre-surgery between complete (95+/-15%), partial (79+/-11%) and non-responders (38+/-42%). TOI changes after the initial therapy stage were strongest in patients with more favorable pathological responses (78%, 56%, and 12% for complete, partial, and non-responders respectively). For patients receiving Bevacizumab (N=9), more detailed serial image analysis of tumor deoxy-hemoglobin revealed short-term changes (7-14 days) where initial decreases in hemoglobin were soon followed by slow increases back to pre-treatment levels. Two of the patients who received Bevacizumab demonstrated detectible residual disease by DOSI after completion of all neoadjuvant therapy, despite that contrast-enhanced MRI signals had disappeared.&amp;#x2028; Discussion: We have provided evidence that DOSI may be well-suited to monitor the response of different cancer drugs, including anti-angiogenic compounds such as Bevacizumab, in breast cancer patients. While the usage of Bevacizumab in human subjects is still under investigation in breast cancer, we foresee that DOSI may be a useful tool in general for the development of drugs and dosing strategies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6056.

Non-invasive detection and monitoring of tumor pathological grade during neoadjuvant chemotherapy by measuring tissue water state using diffuse optical spectroscopic imaging.

Abstract Abstract #803 Background: Changes of tissue water state are related to physiological and pathological properties of breast tissues. For instance, MRI has measured water mobility in order to monitor local micro-structural changes in breast cancer tissues during chemotherapy. Diffuse Optical Spectroscopic Imaging (DOSI) measures water molecular vibrational states associated with macro-molecular complexes in tissues such as proteins. For DOSI measurements, breast tumors are line-scanned and spectral information on each point is spatially mapped to generate an image.&amp;#x2028; Subjects &amp; Methods: DOSI was employed to measure 15 infiltrating ductal carcinoma (IDC) patients before treatment. Five IDC and one infiltrating lobular carcinoma (ILC) tumors were also measured along the course of neoadjuvant chemotherapy. Patient responses were determined from standard pathology: complete (N=2), partial (N=2) and non-responders (N=2). The spectral features of tissue water absorption from 935 nm to 998nm were compared to those of a pure water spectrum measured at body temperature in order to acquire the Bound Water Index (BWI: the residual between tissue and pure water spectra). In spectroscopic images, the Cancer BWI Ratio (CBR) was calculated by counting the fraction of the BWI less than 20% of the BWI range of pre-chemo (baseline) measurement in a primary cancer. Lower BWI means the cancer has more free water. The CBR communicates the changes of tissue water state along the course of therapies in the similar way to Signal Enhanced Ratio (SER) used in contrast enhanced MRI.&amp;#x2028; Results: In our in vivo clinical studies with 15 IDC tumors, a high inverse correlation between BWI and Nottingham Bloom-Richardson histopathological score (R=-0.87) was found. In the neoadjuvant chemotherapy studies, BWI increased during the entire course of the therapy in complete responders while it fluctuated then stayed close to baseline values in partial responders. In non-responders, the change amount of BWI was very small and the BWI values decreased below baseline values. Quantitatively, for complete responders, BWI increased (more bound water) 59% from baseline and CBR decreased (less pixels for cancer) 26.9% and the pixels presenting cancer property disappeared. In partial responders, BWI increased 4.7% and CBR decreased 8.2% whereas, in non-responders, BWI decreased 16.4% and CBR increased 28.7%.&amp;#x2028; Discussion: The high correlation between BWI and histopathological score communicates that water state measurements using DOSI report on disease grades of breast cancer non-invasively. In the neoadjuvant chemotherapy studies, bigger tissue water state changes have been measured in complete than partial responders and the changes to the opposite direction in non-responders. There results demonstrate a potential of tissue water state with DOSI as a non-invasive pathological grade monitor during chemotherapy, which can be used as a substitute for a biopsy at any point during the treatment cycle. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 803.