mri guided trans rectal ultrasound biopsy: a molecular approach to diagnosing prostatic cancer

MRI Guided Trans Rectal Ultrasound Biopsy: A Molecular Approach to Diagnosing Prostatic Cancer

of 18

MRI guided trans rectal ultrasound biopsy: a molecularapproach to diagnosing prostatic cancer

Poster No.: C-1785

Congress: ECR 2013

Type: Scientific Exhibit

Authors: B. Raghavan, A. Wasim, P. Gopalakrishnan, R. BALAJI, J.Govindaraj, M. Logudas; Chennai/IN

Keywords: Genital / Reproductive system male, Oncology, MR-Spectroscopy,Ultrasound, Biopsy, Tissue characterisation

DOI: 10.1594/ecr2013/C-1785

Any information contained in this pdf file is automatically generated from digital materialsubmitted to EPOS by third parties in the form of scientific presentations. Referencesto any names, marks, products, or services of third parties or hypertext links to third-party sites or information are provided solely as a convenience to you and do not inany way constitute or imply ECR's endorsement, sponsorship or recommendation of thethird party, information, product or service. ECR is not responsible for the content ofthese pages and does not make any representations regarding the content or accuracyof material in this file.As per copyright regulations, any unauthorised use of the material or parts thereof aswell as commercial reproduction or multiple distribution by any traditional or electronicallybased reproduction/publication method ist strictly prohibited.You agree to defend, indemnify, and hold ECR harmless from and against any and allclaims, damages, costs, and expenses, including attorneys' fees, arising from or relatedto your use of these pages.Please note: Links to movies, ppt slideshows and any other multimedia files are notavailable in the pdf version of presentations.www.myESR.org

of 18

Purpose

Trans Rectal Ultra Sound gives an idea of the morphology of the prostate gland but itis not a good predictor for malignancy. Though Trans Rectal Ultra Sound is used forobtaining samples for histopathology, the sampling of the prostate gland is a systematicone involving not just the ultrasound detected abnormalities but all areas of the glandeven if they appear normal by ultrasound.

MRI and MR Spectroscopy is morphological and functional imaging and is a betterindicator of malignancy (1). Second-look ultrasound (2) after MRI in breast is doneroutinely to locate the lesion and biopsy under ultrasound guidance as MRI guidedbiopsies in the MRI suite are expensive & time consuming as opposed to the moreefficient ultrasound guided biopsy.

The purpose of this study is to assess the efficacy of second-look Trans- rectal Ultrasoundguided biopsy by comparing the histopathological results obtained by Trans RectalUltra Sound guided extended sextant core biopsy of the prostate done before and afterlocalization of lesions using MRI & MRS done prior to the procedure.

Methods and Materials

The study was conducted as a prospective controlled analytical study at Apollo SpecialityHospital, 320 Padma Complex, Anna Salai, Chennai- 600035.

Out of a total of 60 patients who were referred by the urologist between September 2011and February 2012 for prostate biopsy either due to elevated sPSA , abnormal DRE orsymptoms suggesting prostate cancer, only 52 patients fulfilled the inclusion criteria andwere included.

Inclusion criteria:

• Patientswith elevated sPSA levels (>4.0 ng/dl) or with sudden increase ofsPSA values in two health examinations.

• Abnormal digital rectal examination (DRE),• Associated urinary symptoms include dysuria, increased frequency of

urination or difficulty initiating urine• Patients with history of prostatic enlargement.

Exclusion criteria:

of 18

• Patients who were previously diagnosed and treated for prostate cancer,• Patients with known local or distant metastasis on presentation• Patients who have recently undergone TRUS biopsy of the prostate.

The final study population consisted of 45 patients. Informed consent was obtained fromall the patients prior to the procedure. The patients underwent MRI with MR Spectroscopyfollowed by extended sextant targeted core tissue prostate biopsies, performed underTRUS guidance with reference to suspicious areas on MRI and MR Spectroscopy inaddition to the regular core tissue biopsies.

After adequate bowel preparation and informed consent, the patients underwent T2 highresolution MR imaging of the prostate in axial, sagittal and coronal planes. Spectroscopywas planned with reference to the MR images in all three planes and effort was taken toinclude the entire prostate avoiding the bladder and adjacent structures to reduce signalto noise ratio (SNR) and to confine the voxels within the prostate margins. All images wereanalyzed for changes in signal intensity in the prostate, and spectroscopy was acquiredfrom the entire prostate including the suspicious areas.

Fourier transformation, phase adjustment, frequency adjustment, baseline correction andcalculation of the Cho+Cr/Cit (CCr) ratios were automatically performed. The total examtook approximately 20 to 30 minutes.

MR image Analysis

The T2 weighted images were analyzed for low signal intensity in contrast to the normalhigh signal intensity especially in the peripheral zone as majority (70%) of the tumorsarise from there. The other suspicious nodules with ill defined margins which showedlow signal intensity were also taken into account. Capsular breach and seminal vesicleinvolvement were made note of.

3D MR spectroscopy imaging evaluation

T2-weighted images were taken as the reference images, and voxels with suspectedtumorous lesions were identified. The CCr ratios from the tumorous lesions and from therest of the prostate were tabulated . In case of contamination resulting in non-diagnosticspectroscopy spectrum, manual adjustment of the baseline was attempted. Voxels wereconsidered to be sufficient for analysis if there was adequate visual match between thebaseline and the obtained spectrum.

The classification system described by Kurhanewicz et al was used (3) . In that systemvoxels are considered suspicious for cancer if the ratio of choline and creatine to citrateis at least 2 standard deviations (SDs) higher than the average ratio for the normal voxelswhich are calculated from the control population. Voxels are considered very suspicious

of 18

for cancer if the ratio of choline and creatine to citrate is higher than 3 SDs above theaverage ratio.

TRUS biopsy

The imaging protocol for TRUS included detailed assessment of the prostate and seminalvesicles in both the sagittal and axial planes and estimation of gland volume in grey scaleand color (FIG 1). The prostate was analyzed for morphology the presence of any hypo,iso or hyperechoic lesions. Extended sextant core tissue biopsies were performed underTRUS (FIG 2) guidance by two senior consultant radiologists with more than 20 yearsexperience.

Extended sextant biopsy is being followed in our institution where two samples fromthe upper, three from the mid and two from lower gland are taken from either sides,amounting to a total of 14 tissue samples for each case. Any visible nodule was biopsiedand separately sent for HPE.

Subsequently the T2W MR images were used as reference during TRUS biopsy andsuspicious areas which showed low signal on T2WI and/or had an elevated CCr ratio onspectroscopy were also sampled in addition to the regular extended sextant biopsies byvisual approximation in reference to the anatomic division of the prostate into sextants ,i.e. right and left base, mid-gland, and apex. (FIG 3)

The samples obtained were sent for histopathology examination in separately labelledbottles. The histopathology results were taken as gold standard for analysis.

Images for this section:

of 18

Fig. 1: TRUS of normal prostate

of 18

Fig. 2: Endorectal probe fitted with an adapter that accepts the needle of a spring-loadedbiopsy gun

of 18

Fig. 3: T2W axial and coronal sections of the normal prostate and a normal CCr ratio onMR spectroscopy. Normal TRUS image of the prostate at the mid-gland level with biopsyneedle in the right and left lobe

of 18

Results

Out of the 45 patients who underwent biopsy, 21 patients were diagnosed with prostatecancer from one or more locations and 24 patients were tumor free.

The study comprises a total of 242 loci from the base, mid gland and apex of prostate ofthe 45 patients. All these patients underwent MRI and proton MR spectroscopy followedby TRUS examination and TRUS guided extended sextant biopsy of the prostate.

Results of TRUS

HPE

TUMOR NO TUMOR

TOTAL

POSITIVE 58 36 94

NEGATIVE 30 118 148

TRUS

TOTAL 88 154 242

Estimate 95% CI

Sensitivity 0.641 0.555 to 0.74

Specificity 0.742 0.693 to 0.801

PPV 0.617 0.516 to 0.709

NPV 0.781 0.725 to 0.844

P value <0.001

Results of MRI

Areas which showed low signal intensity on high resolution T2W images were identified.Based on these, spectroscopy was planned and CCr ratios were obtained from the entireprostate and from the areas which were suspicious for tumor.

Out of 242 loci which were studied, hypointense signal suggesting tumor was seen in115 loci on T2W images. 88 of these loci contained tumor on HPE.

Results of Spectroscopy

Of the 242 voxels, 49 voxels which were proven on HPE as normal showed CCr ratios inthe range of 0.16 and 1.16. The mean CCr ratio from the normal prostate was 0.49 ±0.21compared to CCr ratio of 0.75±0.16 obtained in the study by Keisuke Saito et al.(4)

of 18

On the basis of this data the threshold value for the diagnosis of prostate cancer by H-MRS was determined to be #0.91, which is equivalent to the mean +2 SD of the CCr ratiofor a normal prostate in our study. The corresponding threshold value for cancer in thestudy by Keisuke Saito et al was # 1.07 (4).

In 21 patients with prostate cancer, tumor was found in 96 loci on HPE. Of these, 8 locicould not be evaluated due to non-diagnostic spectrum on MR spectroscopy. The meanCCr ratio (+3SD) for a very high suspicion for prostate cancer was calculated to be 1.41±0.75 compared to 1.40±0.20 seen in the study by Keisuke Saito et al (4).

Sensitivity, specificity, positive predictive value, negative predictive value and ROCcurves were calculated from 242 voxels of 45 patients based on the threshold value of#0.91.

MRI and MRS combined

HPE

TUMOR NO TUMOR

TOTAL

POSITIVE 86 27 113

NEGATIVE 2 127 129

Combined MRIand MRS

TOTAL 88 154 242

Estimate 95% CI

Sensitivity 0.977 [0.921 to 0.994]

Specificity 0.825 [0.757 to 0.877]

PPV 0.761 [0.675 to 0.83]

NPV 0.984 [0.945 to 0.996]

P value <0.001

Combining MRI and MRS, the sensitivity, specificity, positive predictive and negativepredictive values in our study were 97.7%, 82.5%, 76.1% and 98.4% which is comparableto Axel Wetter et al, who obtained a combined MRI and MRS statistical data of75%,93%,75% and 93% respectively.(5)

Similarly, the study by E. Squillaci et al combining MRI and MRS too showed a greaterspecificity of 90 %. The sensitivity, positive and negative predictive values were 71, 89and 74 % respectively (6).

MRI & MRS COMBINED

of 18

Sensitivity Specificity Positivepredictivevalue

Negativepredictivevalue

Our study 97% 83% 76% 98%

Axel wetter etal

75% 93% 75% 93%

E. Squillaci etal

71% 90% 89% 74%

Senstivity & Specificity of TRUS ,MRI, MRS

Furthermore, overall TRUS features of the prostate were evaluated and compared withthe HPE results obtained after biopsy and statistical analysis was done (Fig 4). Weobtained a statistically significant sensitivity of 64%, specificity of 74%, positive predictivevalue of 61 % and negative predictive value of 78% which is higher compared to otherstudies which have shown sensitivity and specificity of TRUS guided biopsy to be around40 - 50 % (7). This increase in sensitivity and specificity compared to earlier studies ismainly due to the role of MRI and MRS in localizing the areas suspicious for malignancyon TRUS. Since MRI and MRS combined had a higher statistical significance, thisreflected in better sample yield on TRUS guided prostate biopsy thereby improving theoverall detection of prostate cancer.

Evaluation of TRUS detected nodules :

19 hypo and hyperechoic suspicious nodules were identified on TRUS during theextended sextant biopsy procedure. These nodules were evaluated for echogenicity andvascularity. They were subsequently biopsied separately and sent for HPE (Fig 5).

On HPE, 6 nodules showed the presence of tumor (FIG 6), 9 nodules showed hyperplasia(FIG 7), 2 were normal prostatic tissue , 1 was indeterminate and 1 showed acuteinflammation.

Retrospectively, on spectroscopy analysis of the nodules which were identified on TRUS,5 out of the 6 nodules which showed the presence of tumor had a CCr > 0.91 (i.e +3 SDsfrom normal) . 11 nodules showed a CCr within +1 standard deviation from the normalthreshold value of 0.49 and 3 nodules had a CCr +2 standard deviations from 0.49 (Fig 8).


of 18

Fig. 4

Fig. 5: HPE of 19 nodules identified in TRUS.

of 18

Fig. 6: TRUE POSITIVE MRI shows hypointense peripheral zones with capsular breachon the left. MRS shows elevated CCr ratios from in all voxels including nodules in theperipheral zones, suspicious for carcinoma. TRUS shows ill defined hypoechoic nodulesin both lobes. Adenocarcinoma was seen on HPE in all samples.

of 18

Fig. 7: Benign prostatic hypertrophy on MRI and TRUS with normal CCr ratios on MRS.HPE confirmed BPH

of 18

Fig. 8

of 18

Conclusion

MRI and MR Spectroscopy is a non-invasive procedure which does not require specialhardware and there is no radiation involved. The total time taken for MR imaging of theprostate including MR spectroscopy analysis is around 25 minutes. The addition of MRspectroscopy to the protocol contributes to only 6 minutes of the total scanning time. MRSpectroscopy as a technique has to be standardized for each individual MR unit and thepatient population.

This study is one of the early studies where an attempt has been made to establish thenormal CCr ratios in our population. A CCr ratio threshold value of 0.91 can objectivelydifferentiate between benign and malignant lesions as inferred from this study.We havefound the results of MR spectroscopy to correlate well with histopathology with a highdegree of specificity (83%) and few false positives (3%) (FIG 6) and false negatives (5%)(FIG 7) which are comparable to other studies byAxel Wetter et al andE. Squillaci et al.

However MR Spectroscopy cannot be done in isolation as a stand-alone procedure asanatomical and morphological analysis in identifying the abnormal areas is required.The zonal anatomy, capsular breach, invasion of the seminal vesicles and bladder baseform an important part in local staging. These are analyzed by T2W high resolution MRimaging.

TRUS guidance for prostate biopsy is primarily used as a convenient real time method toperform a meticulous and methodical biopsy avoiding the urethra, seminal vesicles andbladder base. There has been a progressive trend to increase the number of cores takenfrom the prostate in an attempt to increase the sensitivity of cancer detection.

Therefore MR imaging of the prostate combined with MR spectroscopy can be effectivelyused as a modality for detection of prostate cancer and create a more accurate localizingmethod for targeted TRUS guided biopsies. Multi-modality fusion techniques using MRIand MR spectroscopy can increase the accuracy and efficiency of targeted TRUS guidedbiopsies in diagnoses of prostate cancer.


of 18

Fig. 9: MRI showes diffuse hypointensity in both peripheral zones. Cystic areasappearing hyperintense on T2W sequences are seen in the right lobe. MRS showselevated CCr ratios from both peripheral zones, suspicious of carcinoma. TRUS showsheteroechoic areas in both lobes of prostate with no definite cystic areas. HPE showedinflammation with abscess.

of 18

Fig. 10: Normal MRS from entire gland including hypointense foci in left peripheral zoneand right central zone of mid-gland seen on MRI. TRUS showing ill defined nodularhypoechoic areas in both lobes with subsequent biopsy from the nodule in the right lobe.HPE showed adenocarcinoma.

of 18

References

1. Filip G. Claus, Hedvig Hricak, Robert R. Hattery :Pretreatment Evaluationof Prostate Cancer: Role of MR Imaging and 1H MR Spectroscopy ;RadioGraphics 2004;24:S170

2. MR-Directed ("Second-Look") Ultrasound Examination for Breast LesionsDetected Initially on MRI: MR and Sonographic Findings Hiroyuki Abe, RobertA. Schmidt, Rajshri N. Shah, et al; AJR February 2010 vol. 194 no. 2 370-377

3. Kurhanewicz J, Vigneron DB, Hricak H, Narayan P, Carroll P, Nelson SJ.Three-dimensional 1H spectroscopic imaging of the in situ human prostatewith high spatial (0.24 to 0.7 cm3) spatial resolution. Radiology 1996; 198:795-805.

4. Keisuke saito et al :Clinical efficacy of proton magnetic resonancespectroscopy (1H-MRS) in the diagnosis of localized prostate cancer ;ANTICANCER RESEARCH 28: 1900 (2008)

5. Axel Wetter, Tobias A. Eng Darius, Nadjmabadi Klaus Fliessbach, ThomasLehnert, Jessen Gurung, Wolf-Dietrich Beecken, Thomas J. Vog:CombinedMRI and MR Spectroscopy of the Prostate Before Radical ProstatectomyAJR2006; 187:726

6. E. Squillaci, G. Manenti, S. Mancino, M. Carlani, M. Di Roma, V. Colangelo, G.Simonetti.MR Spectroscopy of Prostate Cancer. Initial Clinical Experience.J.Exp. Clin. Cancer Res., 2005; 527

7. Beerlage HP, Aarnink RG, Ruijter ET, et al. Correlation of transrectalultrasound, computer analysis of transrectal ultrasound and histopathology ofradical prostatectomy specimen. Prostate Cancer Prostatic Dis 2001; 4:56-62

Personal Information

Dr.Bagyam Raghavan

Consultant Radiologist

Apollo Speciality Hospitals

Chennai.INDIA

e-mail: [email protected].

Apollo hospitals: http://www.apollohospitals.com/Twitter: https://twitter.com/HospitalsApolloYoutube: http://www.youtube.com/apollohospitalsindiaFacebook: http://www.facebook.com/TheApolloHospitalsSlideshare: http://www.slideshare.net/Apollo_HospitalsLinkedin: http://www.linkedin.com/company/apollo-hospitalsBlog:Blog: http://www.letstalkhealth.in/

mri guided trans rectal ultrasound biopsy: a molecular approach to diagnosing prostatic cancer

Health & Medicine

prostate biopsy

ultrasound guidance

mri guided biopsies

mri suite

mri mrs

prostate gland

prostate c

extended sextant core