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1.  Correction to (2011) 84, e109-e113 doi: 10.1259/bjr/51344661 
The British Journal of Radiology  2011;84(1003):674.
PMCID: PMC3473488
3.  Correction to 2010 83: 811-813 doi: 10.1259/bjr/49490647 
The British Journal of Radiology  2011;84(1001):483.
PMCID: PMC3473644
5.  The value of diffusion-weighted MRI in the diagnosis of malignant and benign urinary bladder lesions 
The British Journal of Radiology  2011;84(1006):875-882.
To investigate the role of diffusion-weighted MRI (DWI) in the diagnosis of urinary bladder (UB) tumours by means of measuring apparent diffusion coefficient (ADC) values.
A total of 83 people aged between 18 and 86 years were included in the study: 63 patients with UB pathology (46 malignant, 17 benign) constituted the case group; 20 individuals without any UB pathology constituted the control group. DWI was applied to all individuals. The ADC values were measured based on the tissue of the UB mass entities and normal UB wall in the control group.
The mean ADC value in the UB carcinoma group was significantly lower than that in the control group: 1.0684 ± 0.26 × 10−3 mm2 s–1 and 2.010 ± 0.11 × 10−3 mm2 s–1, respectively (p<0.01). There was a significant difference among the mean ADC values of different grades of malignant tumours, corresponding to 0.9185 ± 0.20 mm2 s–1 and 1.281 ± 0.18 mm2 s–1 in high-grade and low-grade malignant UB carcinomas, respectively (p<0.01). The ADC value in the carcinoma group was significantly lower than that in the benign lesion group: 1.0684 ± 0.26 × 10−3 mm2 s–1 and 1.803 ± 0.19 × 10−3 mm2 s–1, respectively (p<0.01). All 46 malignant lesions displayed a restriction in diffusion; 4 of the 17 benign lesions displayed a mild restriction in diffusion. The sensitivity, specificity and accuracy of DWI in the diagnosis of malignant UB lesions was 100%, 76.5% and 93.65%, respectively.
DWI can be beneficial in the differentiation of benign and malignant UB lesions, as well as of high-grade and low-grade UB carcinomas, using quantitative ADC measurements.
PMCID: PMC3473772  PMID: 21224296
6.  Differential diagnosis of benign and malignant breast masses using diffusion-weighted magnetic resonance imaging 
Diffusion-weighted magnetic resonance imaging (DW-MRI) is different from conventional diagnostic methods and has the potential to delineate the microscopic anatomy of a target tissue or organ. The purpose of our study was to evaluate the value of DW-MRI in the diagnosis of benign and malignant breast masses, which would help the clinical surgeon to decide the scope and pattern of operation.
A total of 52 female patients with palpable solid breast masses received breast MRI scans using routine sequences, dynamic contrast-enhanced imaging, and diffusion-weighted echo-planar imaging at b values of 400, 600, and 800 s/mm2, respectively. Two regions of interest (ROIs) were plotted, with a smaller ROI for the highest signal and a larger ROI for the overall lesion. Apparent diffusion coefficient (ADC) values were calculated at three different b values for all detectable lesions and from two different ROIs. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of DW-MRI were determined for comparison with histological results.
A total of 49 (49/52, 94.2%) lesions were detected using DW-MRI, including 20 benign lesions (two lesions detected in the same patient) and 29 malignant lesions. Benign lesion had a higher mean ADC value than their malignant counterparts, regardless of b value. According to the receiver operating characteristic (ROC) curve, the smaller-range ROI was more effective in differentiation between benign and malignant lesions. The area under the ROC curve was the largest at a b value of 800 s/mm2. With a threshold ADC value at 1.23 × 10−3 mm2/s, DW-MRI achieved a sensitivity of 82.8%, specificity of 90.0%, positive predictive value of 92.3%, and positive likelihood ratio of 8.3 for differentiating benign and malignant lesions.
DW-MRI is an accurate diagnostic tool for differentiation between benign and malignant breast lesions, with an optimal b value of 800 s/mm2. A smaller-range ROI focusing on the highest signal has a better differential value.
PMCID: PMC4328303
breast lesions; b value; differential diagnosis; diffusion-weighted imaging; magnetic resonance imaging
7.  Histopathological Correlation of Atypical (C3) and Suspicious (C4) Categories in Fine Needle Aspiration Cytology of the Breast 
Introduction. According to the National Cancer Institute (NCI) guidelines in 1996, breast lesions are categorized as C1 to C5 on fine needle aspiration (FNA) cytology. Very few studies are available in the English literature analyzing histopathology outcome of C3 (atypical, probably benign) and C4 (suspicious, probably malignant) lesions. Our study aims to correlate FNA cytology of breast lump diagnosed as C3 and C4 lesion with histopathological examination. Methods. During a period of 2 years, 59 cases of C3 and 26 cases of C4 were retrieved from total 1093 cases of breast FNA. All the cases were reviewed by two cytopathologists independently. The final 24 cases of C3 and 16 cases of C4 categories were correlated with histopathological diagnosis. Result. Among C3 category, 37.5% revealed malignant findings, whereas of C4 category, 87.5% were malignant on histopathology. This difference was statistically significant (P = 0.0017). Sensitivity, specificity, positive predictive values, and negative predictive value of C4 category in diagnosing breast malignancy were 60.8%, 88.2%, 87.5%, and 62.5%, respectively. Conclusion. Although FNAC is simple, safe, cost-effective and accurate method for diagnosis of breast masses, one must be aware of its limitations particularly in C3 and C4 categories. Also, since both these categories carry different probabilities of malignancy and thus different management, we therefore, support maintaining C3 and C4 categories.
PMCID: PMC3794549  PMID: 24175096
8.  PET/CT and MRI in Bladder Cancer 
Journal of cancer science & therapy  2012;Suppl 14(1):7692.
Bladder Cancer (BCa) is the most common malignancy arising from the urinary tract. One of the mainstays of diagnosis, staging, and therapeutic decision-making for BCa is accurate and appropriate imaging. The ability to identify metastatic disease preoperatively is of utmost importance in determining treatment. Advances in standard cross sectional imaging techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) have improved imaging of bladder cancer. Over the last decade, 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) in combination with CT (18F-FDG PET/CT) has become an important non-invasive imaging modality for the preoperative staging of various malignancies. 18F-FDG PET/CT is useful for detection of metastatic disease in BCa, but the ability to detect primary bladder wall lesions remains to be elucidated. To overcome the problem with urinary excretion of 18F-FDG, new PET tracers are being tested. MRI is an accurate technique for the local staging of BCa due to its superior spatial and contrast resolution. Anatomical MRI has a modest utility in NM-staging of BCa. However, incorporation of functional MR techniques, such as diffusion weighted MRI can improve the results for lesion detection and staging and multi-parametric MRI`s role is yet to be explored widely. The aim of this review is to present the recent advances in PET/CT and MRI in BCa, with particular focus on improvements in staging.
PMCID: PMC3587689  PMID: 23471167
Positron Emission Tomography/Computed Tomography (PET/CT); Magnetic Resonance Imaging (MRI); Urothelial cancer; Bladder cancer
9.  Conspicuity of breast lesions at different b values on diffusion-weighted imaging 
BMC Cancer  2012;12:334.
Diffusion-weighted (DW) imaging has shown potential to differentiate between malignant and benign breast lesions. However, different b values have been used with varied sensitivity and specificity. This study aims to prospectively evaluate the influence of b value on the detection and assessment of breast lesions.
Institutional review board approval and informed patient consent were obtained. Between February 2010 and September 2010, sixty women suspected of having breast cancer by clinical examination and mammography underwent bilateral breast MRI and DW imaging (with maximum b values of 600, 800, and 1000 s/mm2). Conspicuity grades of lesions at different b values on DW images were performed. Signal intensity and apparent diffusion coefficient (ADC) values were recorded and compared among different b values by the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and receiver operating characteristic (ROC) curve.
Fifty-seven lesions from 52 recruited patients including 39/57 (68%) malignant and 18/57 (32%) benign were confirmed with pathology. DCE MRI accurately detected 53 lesions with the sensitivity of 93.0% and specificity of 66.7%, and DW imaging accurately detected 51 lesions with the sensitivity of 89.5% and specificity of 100%. There were no significant differences in conspicuity grades compared among the three b values (P = 0.072), although the SNR and CNR of breast lesions decreased significantly with higher b values. Mean ADCs of malignant lesions (b = 600 s/mm2, 1.07 ± 0.26 × 10-3 mm2/s; b = 800 s/mm2, 0.96 ± 0.22 × 10-3 mm2/s; b = 1000 s/mm2, 0.92 ± 0.26 × 10-3 mm2/s) were significantly lower than those of benign lesions (b = 600 s/mm2, 1.55 ± 0.40 × 10-3 mm2/s; b = 800 s/mm2, 1.43 ± 0.38 × 10-3 mm2/s; b = 1000 s/mm2, 1.49 ± 0.38 × 10-3 mm2/s) with all P values <0.001, but there were no significant differences among the three b values (P = 0.303 and 0.840 for malignant and benign lesions, respectively). According to the area under the ROC curves, which were derived from ADC and differentiate malignant from benign lesions, no significant differences were found among the three b values (P = 0.743).
DW imaging is a potential adjunct to conventional MRI in the differentiation between malignant and benign breast lesions. Varying the maximum b value from 600 to 1000 s/mm2 does not influence the conspicuity of breast lesions on DW imaging at 1.5 T.
PMCID: PMC3464932  PMID: 22853049
10.  Evaluation of primary adnexal masses by 3T MRI: categorization with conventional MR imaging and diffusion-weighted imaging 
To investigate the 3.0-Tesla (3 T) magnetic resonance imaging (MRI) characteristics of primary adnexal lesions for discriminating benign from malignant lesions.
One hundred thirty-nine patients with pathologically proven primary adnexal masses referred for 3 T MRI assessment preoperatively were included. Baseline characteristics, components, and conventional MRI and diffusion-weighted imaging (DWI-MRI) signals were recorded and compared.
There were 22 ovarian cysts, 33 endometriomas, 43 benign tumors and 42 malignant tumors. When ovarian cyst and endometrioma were excluded, there were no significant differences in patients’ age between benign and malignant tumor (P = 0.235). There were no significant differences (P = 0.606) in the conventional MRI signals and significant difference (P = 0.008) in DWI-MRI signal between the non-malignant and malignant lesions. There was a significant difference (P = 0.000) in the apparent diffusion coefficient values (ADCs) between the non-malignant and malignant lesions.
3 T MRI categorized the characteristics of primary adnexal lesions. Conventional MRI signals were not useful for characterizing between benign and malignant lesions. DWI-MRI and ADCs were helpful for distinguishing malignant from benign ovarian lesions.
PMCID: PMC3576319  PMID: 23148860
Magnetic resonance images; Diffusion weighted imaging; 3.0 Tesla; Ovary diseases
11.  Does the Novel Integrated PET/MRI Offer the Same Diagnostic Performance as PET/CT for Oncological Indications? 
PLoS ONE  2014;9(3):e90844.
We compared PET/MRI with PET/CT in terms of lesion detection and quantitative measurement to verify the feasibility of the novel integrated imaging modality for oncological applications.
Methodology/Principal Findings
In total, 285 patients referred to our PET/CT center for oncological indications voluntarily participated in this same-day PET/CT and PET/MRI comparative study. PET/CT images were acquired and reconstructed following routine protocols, and then PET/MRI was performed at a mean time interval of 28±11 min (range 15–45 min). PET/MRI covered the body trunk with a sequence combination of transverse T1WI 3D-volumetric interpolated breath-hold, T2WI turbo spin echo with fat saturation, diffusion-weighted imaging with double b values (50 and 800 s/mm2), and simultaneous PET acquisition over 45 min/5 bed positions. The maximum standardized uptake value (SUVmax) was assessed by manually drawn regions of interest over fluorodeoxyglucose-positive lesions. Among 285 cases, 57 showed no abnormalities, and 368 lesions (278 malignant, 68 benign and 22 undetermined) were detected in 228 patients. When stand-alone modalities were evaluated, PET revealed 31 and 12 lesions missed by CT and MRI, respectively, and CT and MRI revealed 38 and 61 more lesions, respectively, than PET. Compared to CT, MRI detected 40 more lesions and missed 8. In the integrated mode, PET/CT correctly detected 6 lesions misdiagnosed by PET/MRI, but was false-negative in 30 cases that were detected by PET/MRI. The overall diagnosis did not differ between integrated PET/MRI and PET/CT. SUVmax for lesions were slightly higher from PET/MRI than PET/CT but correlated well (ρ = 0.85–0.91).
The novel integrated PET/MRI performed comparatively to PET/CT in lesion detection and quantitative measurements. PET from either scanner modality offered almost the same information despite differences in hardware. Further study is needed to explore features of integrated PET/MRI not addressed in this study.
PMCID: PMC3946212  PMID: 24603857
12.  Diffusion-Weighted Magnetic Resonance Diagnosis of Local Recurrences of Prostate Cancer after Radical Prostatectomy: Preliminary Evaluation on Twenty-Seven Cases 
BioMed Research International  2014;2014:780816.
Objectives. To assess the diagnostic performance of diffusion-weighted MR imaging (DWI) in patients affected by prostatic fossa (PF) relapse after radical prostatectomy (RP) for prostatic carcinoma (PC). Methods. Twenty-seven patients showing a nodular lesion in the PF at T2-weighted MR imaging after RP, with diagnosis of PC relapse established by biopsy or PSA determinations, were investigated by DWI. Two readers evaluated the DWI results in consensus and the apparent diffusion coefficient (ADC) of the nodules, separately; a mean value was obtained (ADCm). Results. Relapses did not significantly differ in size in respect of postsurgical benign nodules. The DWI qualitative evaluation showed sensitivity, specificity, accuracy, ppv, and npv values, respectively, of 83.3%, 88.9%, 85.2%, 93.7%, and 72.7% (100%, 87.5%, 95.6%, 93.7%, and 100%, for nodules >6 mm). The intraclass correlation coefficient (ICC) for ADC evaluation between the two readers was 0.852 (95% CI 0.661–0.935; P = 0.0001). The ADCm values for relapses and benign nodules were, respectively, 0.98 ± 0.21 × 10−3 mm2/sec and 1.24 ± 0.32 × 10−3 mm2/sec (P = 0.006). Sensitivity, specificity, accuracy, ppv and npv of ADCm were, respectively, 77.8%, 88.9%, 81.8%, 93.3%, and 66.7% (93.3%, 87.5%, 85.4%, 93.3%, and 87.5% for nodules >6 mm). Conclusions. Diffusion-weighted MR imaging is a promising tool in the management of a hyperintense nodule detected by T2-weighted sequences. This might have a relevant importance in contouring radiotherapy treatment volumes.
PMCID: PMC3947666  PMID: 24695416
13.  Mammographic density, MRI background parenchymal enhancement and breast cancer risk 
Annals of Oncology  2013;24(Suppl 8):viii37-viii41.
Mammographic density (MD), representing connective and epithelial tissue (fibroglandular tissue, FGT) is a major risk factor for breast cancer. In an analysis of an autopsy series (Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification and parenchymal patterns as indicators of histologic “high-risk” benign breast disease. Cancer 1990; 66: 1721–1725, Bartow SA, Pathak DR, Mettler FA et al. Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors. Am J Epidemiol 1995; 142: 813–819), MD was found to be strongly correlated with the collagen and epithelial content of the breast (Li T, Sun L, Miller N et al. The association of measured breast tissue characteristics with MD and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 343–349), and another report showed that breast epithelium was highly concentrated in the areas of collagen concentration (Hawes D, Downey S, Pearce CL et al. Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity. Breast Cancer Res 2006; 8: R24). Collagen comprises the overwhelming majority of the FGT, occupying an area on the slides obtained from the autopsy series some 15 times the area of glandular tissue. The relationship of MD with breast cancer risk appears likely to be due to a major extent to increasing epithelial cell numbers with increasing MD. FGT is also seen in breast magnetic resonance imaging (breast MRI) and, as expected, it has been shown that this measure of FGT (MRI-FGT) is highly correlated with MD. A contrast-enhanced breast MRI shows that normal FGT ‘enhances’ (background parenchymal enhancement, BPE) after contrast agent is administered(Morris EA. Diagnostic breast MR imaging: current status and future directions. Radiol Clin North Am 2007; 45: 863–880, vii., Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic accuracy, and transfer to clinical practice. Radiology 2007; 244: 356–378), and a recent study suggests that BPE is also a major breast cancer risk factor, possibly as important as, and independent of MD (King V, Brooks JD, Bernstein JL et al. BPE at breast MR imaging and breast cancer risk. Radiology 2011; 260: 50–60). BPE is much more sensitive to the effects of menopause and tamoxifen than is FGT (King V, Gu Y, Kaplan JB et al. Impact of menopausal status on BPE and fibroglandular tissue on breast MRI. Eur Radiol 2012; 22: 2641–2647, King V, Kaplan J, Pike MC et al. Impact of tamoxifen on amount of fibroglandular tissue, BPE, and cysts on breast MRI. Breast J 2012; 18: 527–534). Changes in MD and BPE may be most useful in predicting response to chemopreventive agents aimed at blocking breast cell proliferation. More study of the biological basis of the effects of MD and BPE is needed if we are to fully exploit these factors in developing chemopreventive approaches to breast cancer.
PMCID: PMC3894109  PMID: 24131968
breast cancer; breast background parenchymal enhancement; breast MRI; mammographic density
14.  Assessment of 1183 screen-detected, category 3B, circumscribed masses by cytology and core biopsy with long-term follow up data 
British Journal of Cancer  2008;98(7):1182-1190.
Discrete masses are commonly detected during mammographic screening and most such lesions are benign. For lesions without pathognomonically benign imaging features that are still regarded likely to be non-malignant (Tabar grade 3) reliable biopsy results would be a clinically useful alternative to mammographic surveillance. Appropriate institutional guidelines for ethical research were followed. Between Jan 1996–Dec 2005 grade 3B discrete masses detected in the setting of a large, population based, breast cancer screening programme are included. Patient demographics, fine needle aspiration biopsy (FNAB), core and surgical biopsy results are tabulated. The final pathology of excised lesions was obtained. Information regarding interval cancers was obtained from the State Cancer Registry records and also through long term follow-up of clients in subsequent rounds of screening. A total of 1183 lesions, mean diameter of 13.3 mm (±8.3 mm) and mean client age of 55.1 years (±8.8 years) are included. After diagnostic work up, 98 lesions (8.3%) were malignant, 1083 were non-malignant and a final histologic diagnosis was not established in two lesions. In the 27 months after assessment, no interval cancers were attributable to these lesions and during a mean follow up of 54.5 months, available in 84.9% of eligible women, only one cancer has developed in the same quadrant as the original lesion, although the two processes are believed to be unrelated. FNAB performed in 1149 cases was definitive in 80.5% cases (882 benign, 43 malignant) with a negative predictive value (NPV) of 99.8% (880 of 882) and a positive predictive value (PPV) of 95.2% (40 of 42, both intraductal papillomas). Core biopsy was performed in 178 lesions, mostly for indefinite cytology. Core biopsy was definitive in 79.8% cases (57% benign 22% malignant) with a PPV of 100% and NPV of 99.0%. In experienced hands FNAB is an accurate first line diagnostic modality for the assessment of 3B screen-detected discrete masses, providing definitive results in 80.5% of cases. When used as a second line modality, core biopsy had a similarly high rate of definitive diagnosis at 79.8%. The stepwise approach to the use of FNAB and core biopsy would reduce substantially the proportion of cases requiring surgical diagnostic biopsy. Given the low probability of malignancy and the imperative to limit the morbidity associated with cancer screening, the demonstration of the reliability of FNAB as a minimally invasive but highly accurate test for this particular subset of screen-detected lesions has significant clinical utility.
PMCID: PMC2359648  PMID: 18382460
biopsy; breast; mammography; screening
15.  Diffusion-weighted magnetic resonance imaging in management of bladder cancer, particularly with multimodal bladder-sparing strategy 
World Journal of Radiology  2014;6(6):344-354.
Bladder-sparing strategy for muscle-invasive bladder cancer (MIBC) is increasingly demanded instead of radical cystectomy plus urinary diversion. Multimodal therapeutic approaches consisting of transurethral resection, chemotherapy, radiotherapy and/or partial cystectomy improve patients’ quality of life by preserving their native bladder and sexual function without compromising oncological outcomes. Because a favorable response to chemoradiotherapy (CRT) is a prerequisite for successful bladder preservation, predicting and monitoring therapeutic response is an essential part of this approach. Diffusion-weighted magnetic resonance imaging (DW-MRI) is a functional imaging technique increasingly applied to various types of cancers. Contrast in this imaging technique derives from differences in the motion of water molecules among tissues and this information is useful in assessing the biological behavior of cancers. Promising results in predicting and monitoring the response to CRT have been reported in several types of cancers. Recently, growing evidence has emerged showing that DW-MRI can serve as an imaging biomarker in the management of bladder cancer. The qualitative analysis of DW-MRI can be applied to detecting cancerous lesion and monitoring the response to CRT. Furthermore, the potential role of quantitative analysis by evaluating apparent diffusion coefficient values has been shown in characterizing bladder cancer for biological aggressiveness and sensitivity to CRT. DW-MRI is a potentially useful tool for the management of bladder cancer, particularly in multimodal bladder-sparing approaches for MIBC.
PMCID: PMC4072819  PMID: 24976935
Diffusion magnetic resonance imaging; Bladder cancer; Urothelial carcinoma; Chemotherapy; Radiotherapy
16.  Diagnostic assessment by dynamic contrast-enhanced and diffusion-weighted magnetic resonance in differentiation of breast lesions under different imaging protocols 
BMC Cancer  2014;14:366.
The apparent diffusion coefficient (ADC) is a highly diagnostic factor in discriminating malignant and benign breast masses in diffusion-weighted magnetic resonance imaging (DW-MRI). The combination of ADC and other pictorial characteristics has improved lesion type identification accuracy. The objective of this study was to reassess the findings on an independent patient group by changing the magnetic field from 1.5-Tesla to 3.0-Tesla.
This retrospective study consisted of a training group of 234 female patients, including 85 benign and 149 malignant lesions, imaged using 1.5-Tesla MRI, and a test group of 95 female patients, including 19 benign and 85 malignant lesions, imaged using 3.0-Tesla MRI. The lesion of interest was segmented from the raw image and four sets of measurements describing the morphology, kinetics, DW-MRI, and texture of the pictorial properties of each lesion were obtained. Each lesion was characterized by 28 features in total. Three classical machine-learning algorithms were used to build prediction models on the training group, which evaluated the prognostic performance of the multi-sided features in three scenarios. To reduce information redundancy, five highly diagnostic factors were selected to obtain a compact yet informative characterization of the lesion status.
Three classification models were built on the training of 1.5-Tesla patients and were tested on the independent 3.0-Tesla test group. The following results were found. i) Characterization of breast masses in a multi-sided way dramatically increased prediction performance. The usage of all features gave a higher performance in both sensitivity and specificity than any individual feature groups or their combinations. ii) ADC was a highly effective factor in improving the sensitivity in discriminating malignant from benign masses. iii) Five features, namely ADC, Sum Average, Entropy, Elongation, and Sum Variance, were selected to achieve the highest performance in diagnosis of the 3.0-Tesla patient group.
The combination of ADC and other multi-sided characteristics can increase the capability of discriminating malignant and benign breast lesions, even under different imaging protocols. The selected compact feature subsets achieved a high diagnostic performance and thus are promising in clinical applications for discriminating lesion type and for personalized treatment planning.
PMCID: PMC4036635  PMID: 24885156
Diffusion-weighted imaging; Breast mass; Quantitative morphology and texture features; Computer-aided diagnosis; Classifier; Feature subset selection
17.  Role of diffusion MRI in characterizing benign and malignant breast lesions 
The aim of this study was to evaluate the role of MRI based diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) for characterizing breast lesions in Indian patients.
Materials and Methods:
This prospective analysis was performed between October 2006 and June 2008. It includes 200 patients between the ages of 16 and 80 years with solid breast lesions greater than 1 cm in diameter. Of these 200 patients, 80 underwent breast MRI with contrast and DWI. One hundred and twenty patients had only DWI as they had come only for sonomammography. A total of 280 lesions were detected. ADC values were calculated for all the lesions and the highest and lowest values of ADC for benign and malignant lesions were identified. Finally, we compared our findings with those of previous studies.
Two hundred and eight lesions were categorized as benign and 72 lesions were categorized as malignant based on the ADC values. Based on previous data, lesions with ADC values from 1.3 to 1.5 mm2/s were considered benign where as lesions with ADC values ranging between 0.85 and 1.1 mm2/s were considered malignant. Two lesions whose ADC values were in the benign range were proven to be malignant tumors after surgery. This method of using ADC values for the detection of malignant lesions showed a sensitivity of 97.22% and a specificity of 100%. The positive predictive value was 100%.
DWI is a useful technique for characterizing breast tumors, especially for lesions that cannot be adequately characterized by ultrasonography and routine magnetic resonance imaging.
PMCID: PMC2797740  PMID: 19881104
Apparent diffusion coefficient; diffusion; MRI
18.  A Piglet Model for Detection of Hypoxic-Ischemic Brain Injury with Magnetic Resonance Imaging 
Munkeby BH, de Lange C, Emblem KE, Bjørnerud A, Kro GAB, Andresen J, Winther-Larssen EH, Løberg EM, Hald JK. A piglet model for detection of hypoxic-ischemic brain injury with magnetic resonance imaging. Acta Radiol 2008;49:1049–1057.
Early detection of hypoxic-ischemic (HI) injury in the asphyxic newborn is important because present prognostic factors are inadequate. Furthermore, therapeutic interventions may have additional benefit if initiated in time.
To assess whether the use of a combined protocol including conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and proton MR spectroscopy (MRS) could detect pathological findings in a piglet model 7 hours after HI.
Material and Methods
Ten piglets were submitted to HI for 30 min followed by reoxygenation with 21% O2 for 7 hours. MRI at 1.5T was done prior to and 7 hours after the HI. Single-voxel proton MRS was performed, and apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in the basal ganglia. MRS identified N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and lactate (Lac). Histology and microtubule-associated protein 2 (MAP-2) staining was performed in the basal ganglia at the end of the experiment.
Compared to baseline, ADC, NAA/Cho, and NAA/Cr were significantly reduced after 7 hours (P < 0.001, P = 00.01, and P = 00.05, respectively) and FA values were increased (P <0.025). The ratios of Lac/Cho and Lac/NAA were significantly higher after 7 hours compared to baseline (P <0.001). Presence of necrosis correlated well with reduced ADC (RS = 0.91) and presence of Lac (RS = 0.80). Histology and MAP-2 staining showed more than 90% necrosis in eight piglets, 60% in one piglet, and no necrosis in one piglet.
Diffusion MRI and proton MRS can detect HI injury in the piglet brain 7 hours after hypoxia. DWI and MRS can be used to give useful prognostic information. This piglet model may potentially be used to mimic clinical situations and is suitable for further research investigating HI injury.
PMCID: PMC2582156  PMID: 18720081
Animal investigations; brain/brainstem; CNS; MR diffusion/perfusion; MR imaging; MR spectroscopy
19.  Role of New Magnetic Resonance Imaging Modalities in Diagnosis of Orbital Masses: A Clinicopathologic Correlation 
To evaluate the role of diffusion-weighted magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) in the diagnosis of different orbital masses and their advantages over conventional MRI.
Materials and Methods:
The study included 20 patients presenting with proptosis. Every patient was subjected to thorough clinical examination, conventional MRI “T1 weighted, T2 weighted, and postcontrast T1 weighted if needed,” diffusion-weighted MRI, and proton MRS. Orbitotomy was performed, the orbital mass was excised, and histopathological examination was performed.
Diffusion-weighted MRI could differentiate between benign lesions and malignant tumors in 70% of cases; however, overlap occurred in 30% of cases with benign tumors showing restricted diffusion whereas proton MRS could differentiate between benign and malignant tumors in 90% of cases.
Diffusion-weighted MRI and proton MRS can potentially increase the accuracy of diagnosis of orbital masses through in vivo tissue characterization. Magnetic resonance spectroscopy seems to be the more accurate modality.
PMCID: PMC2892136  PMID: 20616927
Magnetic resonance spectroscopy; Neuroimaging; Orbital masses; Proptosis
20.  Correlation of the Apparent Diffusion Coefficient (ADC) with the Standardized Uptake Value (SUV) in Lymph Node Metastases of Non-Small Cell Lung Cancer (NSCLC) Patients Using Hybrid 18F-FDG PET/MRI 
PLoS ONE  2015;10(1):e0116277.
To compare the apparent diffusion coefficient (ADC) in lymph node metastases of non-small cell lung cancer (NSCLC) patients with standardized uptake values (SUV) derived from combined 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI).
Material and Methods
38 patients with histopathologically proven NSCLC (mean age 60.1 ± 9.5y) received whole-body PET/CT (Siemens mCT™) 60min after injection of a mean dose of 280 ± 50 MBq 18F-FDG and subsequent PET/MRI (mean time after tracer injection: 139 ± 26 min, Siemens Biograph mMR). During PET acquisition, simultaneous diffusion-weighted imaging (DWI, b values: 0, 500, 1000 s/mm²) was performed. A maximum of 10 lymph nodes per patient suspicious for malignancy were analyzed. Regions of interest (ROI) were drawn covering the entire lymph node on the attenuation-corrected PET-image and the monoexponential ADC-map. According to histopathology or radiological follow-up, lymph nodes were classified as benign or malignant. Pearson’s correlation coefficients were calculated for all lymph node metastases correlating SUVmax and SUVmean with ADCmean.
A total of 146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes were eligible for final analysis. Ninety-one lymph nodes were classified as malignant and 9 as benign according to the reference standard. In malignant lesions, mean SUVmax was 9.1 ± 3.8 and mean SUVmean was 6.0 ± 2.5 while mean ADCmean was 877.0 ± 128.6 x10-5 mm²/s in PET/MRI. For all malignant lymph nodes, a weak, inverse correlation between SUVmax and ADCmean as well as SUVmean and ADCmean (r = -0.30, p<0.05 and r = -0.36, p<0.05) existed.
The present data show a weak inverse correlation between increased glucose-metabolism and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI thus may offer complementary information for the evaluation of treatment response in lymph node metastases of NSCLC.
PMCID: PMC4289066  PMID: 25574968
21.  The value of diffusion-weighted imaging in assessing the ADC changes of tissues adjacent to breast carcinoma 
BMC Cancer  2009;9:18.
To define a threshold value of apparent diffusion coefficient (ADC) with which malignant breast lesions can be distinguished from benign lesions, and to evaluate the ADC change of peri-tumor tissue in breast carcinoma by echo planar-diffusion weighted imaging (EPI-DWI).
57 breast lesions were scanned by routine MRI and EPI-DWI. The ADC values were compared between malignant and benign lesions. The sensitivity and specificity of EPI-DWI and the threshold ADC value were evaluated by Receiver Operating Characteristic curve (ROC). The ADC values of malignant lesion and layered peri-tumor tissues (from innermost layer 1 to outermost layer 4 with 5 mm every layer) in different directions were compared and the ADC values among different layers were compared.
The ADC value of 35 malignant lesions was statistically lower than that of 22 benign lesions (P < 0.05). In ROC curve, the threshold value was 1.24 +/- 0.25*10E-3 mm2/s (b = 500) or 1.20 +/- 0.25*10E-3 mm2/s (b = 1000). The ADC value of malignant lesions was statistically lower than that of peri-tumor tissues in different directions (P < 0.05). For peri-tumor tissues, the ADC values increased gradually from layer 1 to layer 4 and there was a significant difference between the ADC values of layer 1 and layer 2 (P < 0.05); while from layer 2 outwards, there was no statistical difference among different layers.
ADC value was a sensitive and specific parameter that could help to differentiate benign and malignant breast lesions. ADC changes in tissues adjacent to breast carcinoma could be detected by EPI-DWI, which made EPI-DWI a promising method for helping to determine surgical scope of breast carcinoma.
PMCID: PMC2633008  PMID: 19144163
22.  Characterization of focal liver lesions using quantitative techniques: comparison of apparent diffusion coefficient values and T2 relaxation times 
European Radiology  2012;22(11):2514-2524.
To compare the efficacy of two quantitative methods for discrimination between benign and malignant focal liver lesions (FLLs): apparent diffusion coefficient (ADC) values and T2 relaxation times.
Seventy-three patients with 215 confirmed FLLs (115 benign, 100 malignant) underwent 1.5-T MRI with respiratory-triggered single-shot SE DWI (b = 50, 400, 800) and dual-echo T2TSE (TR = 3,000 ms; TE1 = 84 ms; TE2 = 228 ms). ADC values and T2 relaxation times of FLLs were calculated. Sensitivity, specificity and accuracy of both techniques in diagnosing malignancy were assessed.
The mean ADC value of malignant tumours (1.07 × 10−3 mm2/s) was significantly lower (P < 0.05) than that of benign lesions (1.86 × 10−3 mm2/s ); however, with the use of the optimal cut-off value of 1.25 × 10−3 mm2/s, 20 false positive (FP) and 20 false negative (FN) diagnoses of malignancy were noted, generating 79 % sensitivity, 82.6 % specificity and 80.9 % accuracy. The mean T2 relaxation time of malignant tumours (64.4 ms) was significantly lower (P < 0.05) than that of benign lesions (476.1 ms). At the threshold of 107 ms 22 FP and 1 FN diagnoses were noted; the sensitivity was 99 %, specificity 80.9 % and accuracy 89.3 %.
Quantitative analysis of T2 relaxation times yielded significantly higher sensitivity and accuracy in diagnosing malignant liver tumour than ADC values.
Key Points
• Diffusion-weighted magnetic resonance imaging is increasingly used for liver lesions.
• But ADC values demonstrated only moderate accuracy for differentiation of liver lesions.
• T2 relaxation times yielded higher accuracy in diagnosing malignant liver tumours.
• Both ADC and T2 values overlapped between focal nodular hyperplasia and malignant lesions.
• Nevertheless T2 liver mapping could be valuable for evaluating focal liver lesions.
PMCID: PMC3472073  PMID: 22699872
Magnetic resonance; Echo-planar imaging; Diffusion-weighted imaging; Liver neoplasms; Quantitative analysis
23.  Differentiation of malignant and benign lung lesions with diffusion-weighted MR imaging 
Radiology and Oncology  2012;46(2):106-113.
The aim of the study was to evaluate the role of diffusion-weighted magnetic resonance imaging in the differential diagnosis of lung lesions.
Patients and methods.
Sixty-seven patients with lung lesions (48 malignant, 19 benign) were included in this prospective study. Signal intensities (SIs) were measured in diffusion-weighted MR images that were obtained with b=0, 500 and 1000 s/mm2 values. Apparent diffusion coefficient (ADC) maps were calculated by using images with b=0 and 1000 s/mm2 values. The statistical significance was determined using the Student-t test.
The SIs of malignant lesions were significantly higher than those of benign lesions (p<0.004 for b=0 s/mm2 and p<0.000 for the other b values). Using b=500 s/mm2, SI≥391 indicated a malignant lesion with a sensitivity of 95%, specificity of 73% and positive predictive value of 87%. Using b=1000 s/mm2, SI≥277 indicated a malignant lesion with a sensitivity of 93%, specificity of 69% and positive predictive value of 85%. There was no significant difference between malignant and benign lesions regarding ADC values (p=0.675). There was no significant difference in SIs or ADC values between small cell carcinoma and non-small cell carcinoma. When comparing undifferentiated with well- partially differentiated cancers, SIs were higher with all b values, but the difference was statistically significant only with b=1000 s/mm2 (p<0.04).
Diffusion-weighteted MR trace image SI is useful for the differentiation of malignant versus benign lung lesions.
PMCID: PMC3472932  PMID: 23077446
pulmonary lesions; diffusion-weighted imaging; apparent diffusion coefficient; magnetic resonance imaging
24.  Differentiation of early hepatocellular carcinoma from benign hepatocellular nodules on gadoxetic acid-enhanced MRI 
The British Journal of Radiology  2012;85(1018):e837-e844.
To test new diagnostic criteria for the discrimination of early hepatocellular carcinoma (HCC) from benign hepatocellular nodules on gadoxetic acid-enhanced MRI (Gd-EOB-MRI).
We retrospectively analysed 34 patients with 29 surgically diagnosed early HCCs and 31 surgically diagnosed benign hepatocellular nodules. Two radiologists reviewed Gd-EOB-MRI, including diffusion-weighted imaging (DWI), and the signal intensity at each sequence, presence of arterial enhancement and washout were recorded. We composed new diagnostic criteria based on the lesion size and MRI findings, and then the diagnostic performance was compared with that of conventional imaging criteria with logistic regression and a generalised estimating equation method.
A size cut-off value (≥1.5 cm diameter) and MRI findings of T1 hypointensity, T2 hyperintensity, DWI hyperintensity on both low and high b-value images (b=50 and 800 s mm−2, respectively), arterial enhancement, late washout and hepatobiliary hypointensity were selected as the diagnostic criteria. When lesions were considered malignant if they satisfied three or more of the above criteria, the sensitivity was significantly higher than when making a diagnosis based on arterial enhancement and washout alone (58.6% vs 13.8%, respectively; p=0.0002), while the specificity was 100.0% for both criteria.
Our new diagnostic criteria on Gd-EOB-MRI may help to improve the discrimination of early HCC from benign hepatocellular nodules.
PMCID: PMC3474012  PMID: 22553295
25.  DW-MRI of the urogenital tract: applications in oncology 
Cancer Imaging  2010;10(1A):S112-S123.
Diffusion-weighted magnetic resonance imaging (DW-MRI) appears to hold promise as a non-invasive imaging modality in the detection of early microstructural and functional changes of different organs. DW-MRI is an imaging technique with a high sensitivity for the detection of a large variety of diseases in the urogenital tract. In kidneys, DW-MRI has shown promise for the characterization of solid lesions. Also in focal T1 hyperintense lesions DW-MRI was able to differentiate hemorrhagic cysts from tumours according to the lower apparent diffusion coefficient (ADC) values reported for renal cell carcinomas. Promising results were also published for the detection of prostate cancer. DW-MRI applied in addition to conventional T2-weighted imaging has been found to improve tumour detection. On a 3 T magnetic resonance unit ADC values were reported to be lower for tumours compared with the normal-appearing peripheral zone. The combined approach of T2-weighted imaging and DW-MRI also showed promising results for the detection of recurrent tumour in patients after radiation therapy. DW-MRI may improve the performance of conventional T2-weighted and contrast-enhanced MRI in the preoperative work-up of bladder cancer, as it may help in distinguishing superficial from muscle invasive bladder cancer, which is critical for patient management. Another challenging application of DW-MRI in the urogenital tract is the detection of pelvic lymph node metastases. As the ADC is generally reduced in malignant tumours and increased under inflammatory conditions, reduced ADC values were expected in patients with lymph node metastases.
PMCID: PMC2967148  PMID: 20880781
Diffusion-weighted magnetic resonance imaging; tumours; kidney; bladder; prostate; lymph nodes

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