Changes In Apparent Diffusion Coefficient Values Research Articles

Preliminary study of early response to neoadjuvant chemotherapy after the first cycle in breast cancer: comparison of 1H magnetic resonance spectroscopy with diffusion magnetic resonance imaging

The aim of this study was to assess the efficacy of single-voxel (1)H magnetic resonance spectroscopy (MRS) at 1.5 T to evaluate early responses to neoadjuvant chemotherapy after the first treatment in breast cancer patients and to compare it to measurements of apparent diffusion coefficient (ADC) values derived from diffusion-weighted magnetic resonance imaging (MRI). Nine patients with breast cancer who were scheduled to receive neoadjuvant chemotherapy were recruited. MR examination after the first cycle was scheduled for a few days before the administration of the second dose. Two patients were excluded from the study because their regimen was changed after the first cycle. MRS before chemotherapy demonstrated the presence of choline (Cho) at 3.22-3.23 ppm in six cases and at 3.27 ppm in one case. Diffusion-weighted MRI before chemotherapy demonstrated a localized high-signal lesion in all cases. The change of the integral value of Cho after the first cycle of chemotherapy showed a positive correlation with the change in lesion size (r = 0.91, P = 0.01), whereas no correlation was observed between the change of ADC values after the first cycle and the change in lesion size (r = 0.45, P = 0.32). MRS after the first cycle may be more sensitive to diffusion-weighted MRI to predict the pathological response.

Diffusion-Weighted MRI in Predicting the Efficacy of Neoadjuvant Chemotherapy of Breast Cancer.

Abstract Objective: To approach the apparent diffusion coefficient(ADC) obtained on diffusion weighted imaging (DWI) in predicting the response of breast cancer to neoadjuvant chemotherapy.Methods: 53 locally advanced breast cancer patients participated in this prospective study on neoadjuvant chemotherapy. All patients were treated with weekly neoadjuvant paclitaxel plus carboplatin for 4 cycles. DWI and ADC value were examined before chemotherapy(the first time point), after the first and the forth cycle of chemotherapy(the second and the third time point). Patients were categorized as high responders if their ADC at the second time point were higher by 2 times the standard deviation than the mean pre-chemotherapy ADC, and otherwise the patients were considered as low responders. Logistic regression was conducted to examine the independent factors predictive of clinical complete response(CR) and pathologic complete response(pCR).Results: CR was documented in 13 patients (24.5%); partial response in 36 patients (67.9%); stable disease in 4 patients (7.5%) and no patient had progressive disease. 11 patients(20.8%) have achieved pCR. There was a strong positive correlation between the percentage changes in ADC value at the third time points and the degree of the tumor reduction. A significant increase in ADC value was observed at the second time point compared with the first time point (1.104±0.117×10-3mm2/s, 1.220±0.158×10-3mm2/s, P<0.001), while the decrease of the longest diameter of the tumors measured by physical examination, ultrasound or MRI or the tumor volumn measured by MRI were not (P>0.05). Logistic regression revealed that percentage changes of ADC value at the second time point were significantly associated with CR(P=0.022, hazard ratio[HR] =1.08, 95% confidence interval[CI]: 1.01∼1.16) and pCR(P=0.022, HR =1.11, 95%CI: 1.02∼1.21). The AUC value of the receiver operating characteristic curve were 0.721(95%CI: 0.512∼0.931, P=0.017) and 0.775(95%CI: 0.598∼0.952, P=0.005) in the two diagnostic tests for CR and pCR, and the sensitivity and specificity were 76.9%, 63.6% and 77.5%, 90.5%, respectively. According to categorizing system described above, 10 patients(18.9%) were considered as high responders and 43 patients(81.1%) low responders. 7 patients(70%) of the high responders have achieved clinical CR and pCR while for the low responders there were only 6 patients(14.0%) and 4 patients (9.3%) proven to have CR and pCR. The difference have both reached statistical significance(P=0.001, P<0.001). Logistic regression confirmed that the categorizing system was independently predictive of CR(P=0.006, HR=42.26, 95%CI: 2.86∼624.08) and pCR(P=0.013, HR=25.19, 95%CI: 2.00∼318.91). Taking this categorizing system as a dignostic test, the sensitivity and specificity were 53.8% and 92.5% for CR and 63.6% and 92.9% for pCR, respectively.Conclusions: The change of ADC value obtained on DWI after the first cycle of neoadjuvant chemotherapy occured prior to the morphologic changes of the tumor and at this time ADC value could to some extent predict the efficacy of neoadjuvant chemotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4025.

Navigator respiratory‐triggered diffusion‐weighted imaging in the follow‐up after hepatic radiofrequency ablation—initial results

To evaluate diffusion alterations after hepatic radiofrequency (RF) ablation using a navigator respiratory-triggered diffusion-weighted imaging (NRT-DWI) sequence with regard to potential diagnostic information for detection of local tumor progression (LTP). One hundred forty-eight consecutive follow-up magnetic resonance (MR) examinations of 54 patients after hepatic RF ablation were reviewed. Apparent diffusion coefficient (ADC) values of ablation zones and liver parenchyma were assessed using a single-shot echoplanar imaging sequence with the NRT technique. ADC values of ablation zones and adjacent signal alterations identified in NRT-DWI were analyzed with regard to LTP. Mean ADC values of ablation zones (119.9 +/- 30.5 x 10(-5) mm(2)/sec) and liver (106.3 +/- 21.2 x 10(-5) mm(2)/sec) differed significantly (P = 0.0003). No evident changes in ablations' ADC values over time could be identified. ADC values obtained from the entire ablation zone did not significantly differ regarding the presence of LTP. In 58 examinations, hyperintense areas in the periphery of the ablation zone were detected on the NRT-DWI. Corresponding ADC values were significantly lower in patients with LTP (102.1 +/- 22.4 versus 130.8 +/- 47.6 x 10(-5) mm(2)/sec; P = 0.0124). NRT-DWI is useful in the follow-up imaging after RF ablation. ADC-based evaluation of signal alterations adjacent to the ablation zone may contribute to the identification of LTP and nontumoral posttreatment tissue changes.

Early Detection of Therapeutic Response to Hepatic Arterial Infusion Chemotherapy of Liver Metastases from Colorectal Cancer Using Diffusion-Weighted MR Imaging

The purpose of this study was to investigate whether diffusion-weighted magnetic resonance imaging (DWI) is useful for early detection of the response of hepatic colorectal metastases to hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil (5-FU). The subjects were 12 patients with hepatic colorectal metastases. The indwelling catheter for HAIC was placed in the hepatic artery, and 1000 mg/m(2) 5-FU was given repeatedly once a week. DWI was performed before and 9 days after HAIC. The minimum and mean apparent diffusion coefficient (ADC) values (minADC and meanADC) were measured. The relative change in ADC values (%ADC) and the relative change in tumor size on follow-up CT after 3 months (reduction ratio) were determined. Liver metastases were divided into two groups, responder and nonresponder. The correlation between %ADC and reduction ratio was determined, and %ADC was compared between the two groups. Eleven patients successfully completed HAIC over the 3-month period; 48 metastatic lesions were evaluated. Positive correlations were observed for relative change between %minADC and reduction ratio (r = 0.709) and between %meanADC and reduction ratio (r = 0.536). Both %minADC and %meanADC were significantly greater in the responder group than in the nonresponder group. With the threshold determined as < 3.5%, the receiver-operating curve analysis showed higher sensitivity and specificity values for %minADC (100% and 92.6%, respectively) than for %meanADC (66.7% and 74.1%, respectively). In conclusion, the relative change in minimum ADC values on DWI may be useful for early detection of the response of liver metastases to HAIC with 5-FU.

Evaluating transcatheter arterial chemoembolization for primary hepatic cancer by magnetic resonance diffusion-weighted imaging

Evaluating transcatheter arterial chemoembolization for primary hepatic cancer by magnetic resonance diffusion-weighted imaging

ADC value and diffusion tensor imaging of prostate cancer: Changes in carbon‐ion radiotherapy

To assess the apparent diffusion coefficient (ADC) value and diffusion tensor image (DTI) including fractional anisotropy (FA) of the noncancerous prostate and prostate cancer before and after carbon-ion radiotherapy (CIRT). Nine patients with biopsy-proven prostate cancer underwent 1.5T magnetic resonance (MR) examinations. One patient with benign prostatic hypertrophy and one healthy volunteer were also examined as references. The changes in ADC values and DTI of the entire prostate calculated from b-values of 0 and 700 (s/mm(2)) were estimated between before and after CIRT. ADC values of prostate cancer significantly increased after CIRT by paired t-test (P < 0.01) but those of noncancerous inner gland (IG) and peripheral zone (PZ) showed no significant change. By analysis of variance, significant differences in ADC values were observed among prostate cancer and noncancerous IG and PZ before CIRT (P < 0.05). After CIRT, those significant differences had disappeared. FAs showed no significant differences in any comparisons. DTI showed changes in the direction of the main axis of the tensor in prostate cancer after CIRT. There were changes in ADC and DTI in prostate cancer after CIRT. They may be useful for monitoring prostatic structural changes under radiotherapy.

Diffusion‐weighted magnetic resonance imaging allows monitoring of anticancer treatment effects in patients with soft‐tissue sarcomas

To determine if diffusion-weighted imaging (DWI) can be used as a surrogate marker of tumor response to anticancer therapy in patients with soft-tissue sarcomas. Magnetic resonance imaging (MRI) including echo-planar DWI sequences was performed prospectively in 23 consecutive patients with soft-tissue sarcomas before and after initiation of regional or systemic chemotherapy. The mean interval between initial and follow-up MRI was 56.9 +/- 23.2 days. Tumor volumes were determined by manual segmentation of tumor borders on contrast-enhanced T1-weighted images. The apparent diffusion coefficient (ADC) was calculated from corresponding sections of ADC maps on initial and follow-up DWI. Subsequently, changes in tumor volumes and ADC were correlated using the Pearson correlation coefficient. A high degree of correlation was found when changes in tumor volumes and ADC values were compared (r = -0.925, P < 0.0001), regardless of the effectiveness of anticancer therapy expressed as changes of tumor volume. DWI can be used as a supplement to morphologic imaging for the evaluation of tumor response to anticancer therapy in patients with soft-tissue sarcomas. As cellular changes are expected to precede morphologic changes in treated tumors, DWI performed at an early stage of fractionated therapy may provide unique prognostic information of its effectiveness.

The effects of brain tissue decomposition on diffusion tensor imaging and tractography

There have been numerous high resolution diffusion tensor imaging studies in fixed animal brains, but relatively few studies in human brains. While animal tissues are generally fixed pre-mortem or directly postmortem, this is not possible for human tissue, therefore there is always some delay between death and tissue fixation. The elapsed time between death and tissue fixation, the postmortem interval (PMI), will most likely adversely affect the tissue's diffusion properties. We studied the effects of PMI on the diffusion properties of rodent brain. Eight mice were euthanized and the brains (kept in the skull) were placed in formalin at PMIs of 0, 1, 4 and 14 days. Post fixation they were placed in a solution of GdDTPA and phosphate buffered saline. Brains were scanned with a 3D EPI DTI sequence at 4.7T. DTI data were processed to generate apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps. DTI tractography was also performed. The temporal changes in regional ADC and FA values were analyzed statistically using a one-way ANOVA, followed by individual Student's T-tests. Regional FA and ADC of gray and white matter decreased significantly with time (p<0.05). DTI tractography showed a decrease in the number and coherence of reconstructed fiber pathways between PMIs 0 and 14. Elapsed time between death and tissue fixation has a major effect upon the brain's diffusion properties and should be born in mind when interpreting fixed brain DTI.

Functional MR Imaging Assessment of Tumor Response after 90Y Microsphere Treatment in Patients with Unresectable Hepatocellular Carcinoma

To assess the utility of functional contrast medium-enhanced and diffusion-weighted magnetic resonance (MR) imaging in the assessment of early (1 month) response of unresectable hepatocellular carcinoma (HCC) to a single treatment with yttrium-90-labeled microspheres. The authors evaluated the MR images obtained before and 1 month after single selective (90)Y microsphere treatment in 13 consecutive patients (mean age, 62 years). All patients had cirrhosis and pathologically proved HCC. Images were evaluated by consensus of two radiologists. Tumor size, arterial and venous enhancement, and apparent diffusion coefficient (ADC) were recorded before and after treatment. One targeted tumor in the treated lobe of the liver was included in each patient. In patients who also had lesions in the contralateral lobe of the liver, a second tumor was included as nontargeted tumor. There were 19 tumors in the 13 patients (mean tumor size, 9.4 cm). The mean tumor burden was 25% of the total liver volume. Targeted tumors (n = 13) demonstrated a mean decrease in arterial enhancement of 22% (P = .013), a mean decrease in venous enhancement of 25% (P = .012), and a mean increase in ADC value of 18% (P < .001). These targeted tumors did not change significantly in size after treatment (P = .492). Six patients had contralateral nontargeted tumors. These nontargeted tumors had no significant change in size (P = 0.100), arterial enhancement (P = .182), venous enhancement (P = .182), or ADC value (P = .105) after treatment. Early after treatment with (90)Y microspheres, tumors demonstrated a decrease in enhancement and an increase in ADC, without a statistically significant change in tumor size. These MR findings are useful in the early posttreatment period for assessing treatment response.

Monitoring therapeutic responses of primary bone tumors by diffusion-weighted image: initial results

The purpose of our study was to investigate whether quantitative diffusion-weighted images (DWI) were useful for monitoring the therapeutic response of primary bone tumors. We encountered 18 osteogenic and Ewing sarcomas. Magnetic resonance (MR) images were performed in all patients before and after therapy. We measured the apparent diffusion coefficient (ADC) values, contrast-to-noise ratio (CNR), and tumor volume of the bone tumors pre- and posttreatment. We determined change in ADC value, change in CNR on T2-weighted images (T2WI), change in CNR on gadopentetate dimeglumine (Gd)-T1-weighted images (Gd-T1WI), and change in tumor volume. The bone tumors were divided into two groups: group A was comprised of tumors with less than 90% necrosis after treatment and group B of tumors at least with 90%. Changes in ADC value, tumor volume, and CNR were compared between the groups. Change in the ADC value was statistically greater in group B than that in the group A (p = 0.003). There was no significant difference in the changes in CNR on T2WI (p = 0.683), in CNR on Gd-T1WI (p = 0.763), and tumor volume (p = 0.065). The ADC value on DWI is a promising tool for monitoring the therapeutic response of primary bone sarcomas.

Preliminary Results on the Influence of Chemoradiation on Apparent Diffusion Coefficients of Primary Rectal Carcinoma Measured by Magnetic Resonance Imaging

To study changes of the apparent diffusion coefficient (ADC) measured by magnetic resonance imaging (MRI) in patients with primary rectal carcinoma during a course of combined chemoradiation. Diffusion-weighted echo-planar imaging at 1.5 T was performed in patients (n = 8) with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation. Mean tumor ADC values and ADC histograms were determined and compared weekly during the course of therapy. Surgical resection of the tumors enabled a correlation of ADC values with the pathologic classification. In four patients tumor T-downstaging (ypT0-2) was observed, and in four patients no downstaging (ypT3) was seen. In all patients, ADC values were higher before onset of chemoradiation therapy compared to the end of chemoradiation. Separating the patients into two groups, a significant increase in ADC value during week 1 of therapy, followed by a steady decrease, was found for the therapy-responder group. In the nonresponder group, no initial increase of ADC values was observed. After the 1st week of therapy, ADC values were significantly lower in the nonresponder group during the remaining duration of therapy. With these preliminary results it could be shown that MR diffusion imaging is able to detect individual changes of tumor ADC values during the course of combined chemoradiation reflecting biological changes within the tumor tissue. Further studies will be necessary to prove the possible value of totally noninvasive ADC imaging on predicting therapy outcome.

Prediction of secondary ischemic lesions with diffusion-weighted imaging after transient middle cerebral artery occlusion in rats

P75 Background and Purpose: Previous studies demonstrated that secondary ischemic lesions documented by diffusion-weighted imaging might be smaller than, larger than or similar to initial lesions that occur during ischemia. The purpose of this study was to investigate if the size of secondary lesions can be predicted. Methods: Twelve rats underwent 30 minutes of transient middle cerebral artery occlusion with the intraluminal suture method. Diffusion- and perfusion-weighted images were performed just before reperfusion, 90 minutes and 24 hours after reperfusion. The ischemic lesion size was calculated by tracing visual abnormalities on the apparent diffusion coefficient (ADC) maps. Cerebral blood flow index (CBF i ) ratio was calculated by dividing the ipsilateral CBF i by the contralateral CBF i . Based on difference between initial and secondary lesion volume, rats were assigned to reperfusion-benefit group (n=6) where secondary lesions were smaller than initial lesions (less than 85% of initial lesions) and reperfusion-nonbenefit group (n=6) where secondary lesions were similar to or larger than initial lesions (more than 85% of initial lesions). Results: At 90 minutes after reperfusion, the initial ischemic lesions almost disappeared in both groups. At 24 hours, secondary lesions were 54±11% (mean±SD) of the initial lesions in the reperfusion-benefit group and 100±14% of the initial lesions in the reperfusion-nonbenefit group (p&lt;0.001). There was no difference in ADC values (47±2×10 -5 mm 2 /s vs 46±5×10 -5 mm 2 /s, p=0.7) and CBF i ratio (0.62±0.06 vs 0.67±0.04, p=0.2) between the two groups before reperfusion. However, the initial lesion volume was significantly smaller in the reperfusion-benefit group than in the reperfusion-nonbenefit group (125±54 mm 3 vs 195±36 mm 3 , p=0.037). Conclusions: Changes of ADC values and CBF before reperfusion are unable to predict if initial ischemic lesions will eventually shrink or not after reperfusion. Smaller size of initial lesions may suggest that secondary lesions will be smaller than initial lesions.

Human acute cerebral ischemia: detection of changes in water diffusion anisotropy by using MR imaging.

To (a) determine the optimal choice of a scalar metric of anisotropy and (b) determine by means of magnetic resonance imaging if changes in diffusion anisotropy occurred in acute human ischemic stroke. The full diffusion tensor over the entire brain was measured. To optimize the choice of a scalar anisotropy metric, the performances of scalar indices in simulated models and in a healthy volunteer were analyzed. The anisotropy, trace apparent diffusion coefficient (ADC), and eigenvalues of the diffusion tensor in lesions and contralateral normal brain were compared in 50 patients with stroke. Changes in anisotropy in patients were quantified by using fractional anisotropy because it provided the best performance in terms of contrast-to-noise ratio as a function of signal-to-noise ratio in simulations. The anisotropy of ischemic white matter decreased (P = .01). Changes in anisotropy in ischemic gray matter were not significant (P = .63). The trace ADC decreased for ischemic gray matter and white matter (P < .001). The first and second eigenvalues decreased in both ischemic gray and ischemic white matter (P < .001). The third eigenvalue decreased in ischemic gray (P = .001) and white matter (P = .03). Gray matter is mildly anisotropic in normal and early ischemic states. However, early white matter ischemia is associated with not only changes in trace ADC values but also significant changes in the anisotropy, or shape, of the water self-diffusion tensor.

Multislice diffusion mapping for 3-D evolution of cerebral ischemia in a rat stroke model.

Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively demonstrate cerebral ischemia within minutes after the onset of ischemia. The use of a DWI echo-planar multislice technique in this study and the mapping of the apparent diffusion coefficient (ADC) of water, a reliable indicator of ischemic regions, allow for the detection of the three-dimensional (3-D) evolution of ischemia in a rat stroke model. We evaluated 13 time points from 5 to 180 minutes after occlusion of the middle cerebral artery (MCA) and monitored the 3-D spread of ischemia. Within 5 minutes after the onset of ischemia, regions with reduced ADC values occurred. The core of the lesion, with the lowest absolute ADC values, first appeared in the lateral caudoputamen and frontoparietal cortex, then spread to adjacent areas. The volume of ischemic tissue was 224 +/- 48.5 mm3 (mean +/- SEM) after 180 minutes, ranging from 92 to 320 mm3, and this correlated well with the corrected infarct volume at postmortem (194 +/- 23.1 mm3, r = 0.72, p < 0.05). This experiment demonstrated that 3-D multislice diffusion mapping can detect ischemic regions noninvasively 5 minutes after MCA occlusion and follow the development of ischemia. The distribution of changes in absolute ADC values within the ischemic region can be followed over time, giving important information about the evolution of focal ischemia.

MRI diffusion mapping of reversible and irreversible ischemic injury in focal brain ischemia

The reduction of the apparent diffusion coefficient (ADC) of water shortly after a focal ischemic insult is thought to reflect intracellular water accumulation (cytotoxic edema) related to high-energy metabolism failure and loss of ion homeostasis. We attempted to clarify whether varying ranges of ADC measurements in ischemic brain tissue can be used to differentiate between reversible and irreversible ischemic lesions before reperfusion in a temporary ischemia model. We induced 45 minutes of temporary ischemia in 12 rats using the middle cerebral artery suture occlusion method. Regional changes of ADC values were serially measured in seven regions of interest in each hemisphere and evaluated by delta ADC, defined as the difference between ADC value in an ischemic region and that in a contralateral homologous region. We acquired dynamic contrast-enhanced perfusion images 2 minutes before and after reperfusion to document reduced perfusion and its restoration. We confirmed the infarct area by 2,3,5-triphenyltetrazolium chloride staining 24 hours after occlusion and correlated this with the MRI studies. Recovery of initially reduced ADC values occurred only in ischemic regions where delta ADC values were not below -0.25 x 10(-5) cm2/sec. Although the extent of infarction at postmortem examination varied in regions with moderately decreased prereperfusion ADC values, more than 70% of regions of interest with slight declines of prereperfusion ADC values exhibited no infarction. ADC values progressively decreased after reperfusion in regions that initially had severely decreased prereperfusion ADC values, and postmortem examination always demonstrated infarction in such regions.(ABSTRACT TRUNCATED AT 250 WORDS)