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From AUA2013: “Histoscanning”- aided template biopsies for patients with previous negative TRUS biopsies

Reporter: Dror Nir, PhD

This year’s AUA takes place in San Diego, USA.

Wednesday, May 08, 2013 10:30 AM-12:30 PM
SDCC: Room 8
Prostate Cancer: Detection & Screening (V)
Moderated Poster
Funding: none
2209: “Histoscanning”- aided template biopsies for patients with previous negative TRUS biopsies.
Oleg Apolikhin; Andrey Sivkov; Gennady Efremov; Nikolay Keshishev; Oleg Zhukov; Andrey Koryakin

Abstract: 2209
Introduction and Objectives
One of the biggest problems in the diagnosis of prostate cancer (PCa), which distinguishes it from many other solid tumors, is the difficulty of tumor imaging by means of standard visualization techniques. A transrectal ultrasound (TRUS) biopsy is mostly performed on the basis of risen PSA and is often blind – tissue specimens are taken from standard zones. Biopsy under MRI control is technically and logistically complicated and expensive, while TRUS can`t always differentiate the suspicious areas. A TRUS-based innovative technique, “Histoscanningâ€� is used in our centre for PCa identification and targeted biopsy.

Methods
Prior to template biopsy we have performed Histoscanning to 31 patients, with previous one to six negative TRUS biopsies and persistent clinical suspicion of PCa (elevated PSA, high-grade prostatic intraepithelial neoplasia (HPIN) in 4 cores or suspicious TRUS findings). Age range was 51 – 75, with PSA values 3,8 – 14,3 ng/ml. Prostate size range 22-67cc. Most of the patients (n-26) from this group received therapy with 5α-reductase inhibitors for 6 months or more. Depending on the gland size, 10-14 standardized cores were taken + 4 additional cores from the suspicious zones marked on Histoscanning report.

Results
Histopathology identified PCa in 13 out of 31 patients , adenocarcinomas with Gleason score ranging 6-8. In 11 patients with no signs of PCa we found HPIN or low-grade PIN. Comparing histology reports with Histoscanning mapping, in 8 PCa cases we found high correlation of this method with histopathological study on the amount and location of tumor lesions and in 5 cases Histoscanning showed greater spread of lesions, with good correlation of the tumor location.

Conclusions
Due to the effectiveness, ease of use and the short time required for data processing, Histoscanning is a promising method for more effective targeted biopsy of the prostate.

As a result of ongoing research, we aim to evaluate sensitivity and specificity of the method, fuse it with MRI, to create a 3D model for biopsy or surgery. In the future, this data could be used for decision making on the nerve-sparing prostatectomy and minimally invasive focal treatments such as cryoablation, high-intensity focused ultrasound, radiofrequency or laser ablation.

Date & Time: May 8, 2013 10:30 AM
Session Title: Prostate Cancer: Detection & Screening (V)
Sources of Funding: none

Personal note:

On the authors’ intention to fuse HistoScanning with MRI: The authors report a very compelling clinical benefit just from using HistoScanning for guiding their biopsies. HistoScanning itself results in a 3D mapping of the prostate and the suspicious locations inside.

3D mapping of the prostate by HistoScanning analysis following motorised TRUS. the colored locations represents tissue suspicious for being cancer.

3D mapping of the prostate by HistoScanning analysis following motorised TRUS. the colored locations represents tissue suspicious for being cancer.

Fusing ultrasound & MRI images is prone to image-registration errors (e.g. due to differences in the prostate’s shape-distortion by the probe) which are larger than the accuracy sought for when performing biopsy or nerve-sparing surgery. I recommend anyone who wishes to guide biopsies and treatment based on MRI and therefore is in need for good level of localized-MRI interpretation, to rely on dedicated MRI interpretation applications and not intra-modalities image fusion.

In addition, major benefits of using HistoScanning for managing prostate cancer patients are the accessibility; A urologist can perform himself, at any time he chooses and at any place, simplicity; it only requires routine TRUS, patient-friendly; it lasts less than a minute and does not require anesthesia and low-cost; it’s ultrasound! Mixing HistoScanning with MRI will certainly eliminate these.

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On the road to improve prostate biopsy

Author-Writer: Dror Nir, PhD

Urologists are in constant search for a method that will improve the outcome of prostate biopsy, particularly when it comes to ruling-in and ruling-out clinically significant prostate cancer. As stated in my recent post – State of the art in oncologic imaging of Prostate; “The disease’s staging and related prognosis are determined during diagnosis based on PSA level and the Gleason score of biopsy’s samples. Although prostate-specific antigen (PSA) screening resulted in the diagnosis of prostate cancer at earlier stages and with lower Gleason scores, it has also contributed to concerns about over-diagnosis, overtreatment of clinically insignificant disease, associated treatment-related toxicity, and escalating costs”. I already reported in the past on research conduc ted in this area; New clinical results supports Imaging-guidance for targeted prostate biopsy and Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-guided intervention? Today I report on recent publication presenting the advantage of using targeted trans-perineal biopsy following HistoScanning imaging instead of systematic TRUS biopsies: Computer-aided (HistoScanning) Biopsies Versus Conventional Transrectal Ultrasound-guided Prostate Biopsies: Do Targeted Biopsy Schemes Improve the Cancer Detection Rate? (Moritz F. Hamann, Claudius Hamann, Eckhard Schenk, Amr Al-Najar, Carsten M. Naumann, and Klaus-Peter Jünemann, Urology, Volume 81, Issue 2, February 2013, Pages 370-375)

I have mentioned HistoScanning (ultrasound-based tissue characterization technology which I have invented and developed to a medical device) in many of my previous posts. HistoScanning for prostate is a specific HistoScanning application that is applied to the ultrasound’s raw signal (not the image) following a comprehensive scan of the prostate capturing its entire volume. The whole process takes about ten minutes and the output is a digital 3D map of the prostate gland where locations suspicious of presenting with prostate cancer are indicated.

HistoScanning report with 2, bilateral, basal lesions.

HistoScanning report with 2, bilateral, basal lesions.

 

The urologist translates such map into a “prostate regional biopsy scheme” when planning his biopsies and direct the needle, under ultrasound guidance, to these predefined suspicious locations.

 The systematic biopsy patterns targeted 7 sectors bilaterally: transition zone, apex, center, and base, each medially and laterally.

The systematic biopsy patterns targeted 7 sectors bilaterally: transition zone, apex, center, and base, each medially and laterally.

In that sense, the workflow is similar to using MRI for tumor detection and creating a tumor map for targeting the biopsy.

As reasoning for conducting the study the investigators argue that: “Exact staging of prostate cancer before treatment is essential for relevant therapeutic decision making. Current procedures, such as nerve-sparing prostatectomy and brachytherapy, as well as active surveillance and future focal treatment options, depend on the reliable identification of cancerous lesions within the prostate. Systematic prostate biopsies with at least 10 to 12 cores are the current standard method to detect and locate significant prostate cancer, as scientific evidence during the last decades has shown. Nevertheless, there are no homogeneous data concerning the required number of cores and the technical approach of prostate biopsy procedures. The unstable histologic results on active surveillance and the well-known discrepancy between transrectal diagnostics and radical prostatectomy specimens underline the neces­sity to develop reliable diagnostic tools for precise detection and localization of prostate cancer. Recent data on HistoScanning computer-aided ultra-sonography have shown favorable results. To generate a greater diagnostic yield than systematic needle biopsies, we integrated HistoScanning-guided targeted biopsies in our general prostate biopsy regimen. We report the cancer detection rate in a prospective series of 80 patients.”

The study’s objective was: “To define potential improvement in prostate cancer detection by application of a computer-aided, targeted, biopsy regimen using HistoScanning.”

Materials and Methods: “The data were collected prospectively from 80 men who consecutively underwent a systematic 14-core prostate biopsy supplemented by targeted transrectal and perineal ultrasound-guided biopsies. All biopsies were performed between March 2011 and September 2011. Indications for prostate biopsy were suspicious findings at the digital rectal examination (DRE), or serum prostate-specific antigen (PSA) level >10 ng/mL, or both. In case of elevated serum PSA levels >4 ng/mL a PSA-velocity of >0.75 ng/mL p.a. and free-to-total PSA ratio <15% were seen as the indication for prostate biopsies. Thirty-six patients had undergone a previous transrectal prostate biopsy. All patients were informed of the mode of the extended prostate biopsy scheme and its potential complications. All patients provided written informed consent for the procedure.After indication and before starting the biopsy procedure, all patients underwent a standardized 3-dimensional (3D) transrectal ultrasound (TRUS) with an end-fire array of a BK 8818 probe. Computer-aided analysis of the raw (radio-frequency) back-scatter data was performed by using the Conformite Europeene-marked and commercially available HistoScanning device, admitted for medical use in the Euro­pean Union (software version 2.1, Advanced Medical Diag­nostics, Belgium).”

“Each patient was diagnosed preoperatively by HistoScanning, defining a maximum of 3 suspicious areas. These areas were biopsied, both transrectally and via the perineum, with a maximum of 3 cores per location.”

Results: “We detected prostatitis in 30 patients (37.5%), premalignant lesions in 10 (12.5%), and prostate cancer in 28 (35%). The transrectal technique was used to detect 78.6% of all cancers using 14 cores by systematic biopsy. With a maximum of 9 targeted cores, 82.1% of all cancers were detected with the targeted perineal approach and 53.6% were detected with the targeted transrectal approach. Although our data did not show significant difference in the performance of targeted transperineal compared with systematic transrectal biopsies, the detection rate of targeted transrectal biopsies was significantly lower.”

 table

Conclusion: “The presented targeted biopsy scheme achieved an overall detection rate of 85% of prostate-specific antigen–relevant pathologic lesions within the prostate. Thus, the presented procedure shows an improved detection rate compared with standard systematic prostate biopsies, and the number of cores required is reduced. Furthermore, the perineal HistoScanning-aided approach seems to be superior to the transrectal approach with respect to the prostate cancer detection rate. The presented procedure might be a step toward reliable ultrasound-based tissue characterization and toward fulfilling the requirements of novel therapeutic strategies.”

 

The authors’ included an elaborated discussion on the background to their study and its results. This discussion is important for understanding the limitation of the study results and for putting the authors conclusion into balanced context: “When other solid-organ cancer guidelines are compared with prostate cancer guidelines, the common methods of prostate cancer detection are unmasked as an outmoded concept because cancer detection is based on chance as a result of a blinded, subjective examination. A systematic biopsy with at least 10 to 12 cores is considered the standard procedure in prostate cancer diagnostics to date. 1,2 The continuous increase in the number of biopsy cores taken over the last years has predictably improved the detection rate, but several studies report detection rates of only 30% to 40% even in repeated biopsies. 5,9 It is noteworthy that the recommendations must be seen as a compromise bbetween the cancer detection rate and the invasiveness of the surgical procedure. Modern diagnostic procedures, including magnetic resonance imaging, elastography, computerized analysis of TRUS/artificial neuronal network analysis, and HistoScanning, try to overcome this principle of approach.7,10,11 The current therapeutic concepts and further currently evolving therapy strategies depend on sophisticated prostate cancer diagnostics. It is more important than ever to look for ways to detect and locate the cancer before subjecting patients to more or less invasive procedures as the indication for surgical treatment or prostate-preserving (focal) tumor therapy. The results of magnetic resonance imaging for prostate cancer detection are very promising so far and show a sensitivity of up to 80%. Elastography has also shown promising capabilities for cancer detection, with a recent review article reporting that several studies show 74% to 75% sensitivity.11 HistoScanning has shown 93% sensitivity in detecting and locating prostate cancer. 12 As a matter of principle, our study is unable to report on the accuracy or sensitivity of prostate cancer detection because the exact number of cancer lesions in our patients collective remains incomputable. Integration of HistoScanning for guided, targeted biopsies helped us achieve a prostate cancer detection rate of 35%. These data are lower than results from current publications on initial prostate biopsies but higher than those of repeated biopsy protocols.4,5,13 Given that tumors looked for during initial biopsies are usually large and easy to detect, we believe that this finding is caused by the smaller overall risk of cancer in a repeated biopsy setting, as was the case in 37.5% of our patients (0.61 biopsies per patient). Overall, HistoScanning seems to improve selective targeting of suspicious prostate lesions. Taking into account all malignant, premalignant, and atypical histologic findings, including prostate cancer, atypical small acinar proliferations, and high-grade prostatic intraepithelial  eoplasia, the detection rate of relevant prostatic lesions by specimens from perineal-targeted biopsies rises to 47.5% and 85%, including prostatitis, respectively. Apart from the high quality of the HistoScanning tissue analysis, we believe in a significant effect of the technical approach used to perform the biopsy. As our data show, prostate cancer detection rates from specimens obtained from perineal-targeted biopsies differed significantly from the transrectal-targeted biopsy regimen, a difference that occurred independently from previous tissue analysis because both targeted approaches are aligned to the same scanning process. Compared with the transrectal approach, the perineal biopsy technique might reduce variables that can influence the needle placement. Furthermore, longitudinal biopsy punches following the axis of the prostate seem to allow more accurate sampling of the anterior part. Theoretically, because previous studies reported inhomogeneous results comparing transrectal and transperineal prostate biopsies.3,4,13 The use of a 14-gauge needle in perineal biopsies might be responsible for a systematic bias because it possibly yields more tissue than transrectal cores. Despite this potential advantage, systematic transrectal biopsies do not reflect a significant difference in the detection rate. Nevertheless, due to the individual setting, our study is unable to report standardized results on the accuracy of comparing transrectal and transperineal needle placement. Template-guided mapping biopsies have recently attracted attention because of the high rate of cancer detection as initial (75%) and even repeat biopsy procedures (46%). 14 It notably increases the ability to locate and differentiate cancer foci within the prostatic gland, implicating mapping biopsies for active surveillance or focal treatment purposes regardless of the considerable surgical trauma generated by the use of extended biopsy protocols. A reduction of tissue trauma by generating a greater diagnostic yield would be a favorable methodologic aspect as initiated by our study. Regarding cancer detection, the presented data show no significant differences between the perineal-targeted and transrectal-targeted systematic biopsy regimen, but even though considerably fewer tissue samples (14 vs 9 cores; -35%) were taken from selected prostate areas, we detected no significant limitations by the perineal approach. These data are even more encouraging when bearing in mind that the number of samples represents a crucial factor in prostate cancer detection rates, as recently reported. A critical issue in the present study is in the implementation of the modified biopsy procedures. Although the surgeons at our center are experienced in using TRUS, our data show a learning curve during the first 80 procedures. In addition, the overlaying of the HistoScanning image analysis to the B-mode grey-scale live ultrasound picture is done by the surgeon performing the biopsy. This process implies a bias in individual interpretation of the TRUS picture and manual needle guidance. The online fusion of HistoScanning with the ultrasound image presumably would increase the handling accuracy. Further methodologic limitations lie in the heterogeneous and small collective of patients that were included in the study. With regard to the reasonably high number of previous negative biopsy specimens, patient selection can affect the hit rate of positive biopsy specimens. This circumstance might make the cancer detection frequency with HistoScanning look relatively small in this particular study compared with other diagnostic methods in patients undergoing an initial biopsy, but this is due to the daily routine in an academic referral center.

For completeness of this reporting and before stating my own conclusion I bring here below two comments that were made, one by Dr. Stephen Jones of Glickman Urological and Kidney Institute, Cleveland, Ohio and the reply by the first author:

COMMENT

The promise of image-guided diagnosis and management of prostate cancer has been frustratingly elusive. Early pioneers of prostate ultrasound imaging reported that hyperechoic lesionswere indicative of malignancy, but it rapidly became clear that the opposite was actually more realistic. Even so, these hypoechoic lesions were soon shown to be poor indicators of prostate cancer. Thus, the value of visual abnormalities on grey-scale prostate ultrasound imaging remains essentially negligible with current technology. As a result, a number of alternative imaging modalities have been developed and introduced with great excitement. Typically, images in the publications showcase an apparently obvious cancer standing out in contrast to adjacent benign tissues. Unfortunately, the data still reveal minimal value from most of these technologies, and those reported in this article are similarly disappointing. HistoScanning demonstrated interesting color images, but coupled with a transperineal-targeted biopsy found exactly one more case of prostate cancer than did the current standard of care—the 14-core extended transrectal biopsy. This “difference” is actually statistically identical (P >.99). Exactly the same number of patients (n¼ 4) was found exclusively by both transperineal HistoScan-targeted biopsy as with standard transrectal biopsy, and when targeted using the transrectal approach, the technology actually missed almost half of the cancers that were identified overall. Furthermore, these data do not support the suggestion that 9 cores are less morbid or traumatic than 14 cores, and the literature is replete with reports demonstrating this is simply not true. This is especially misleading when those 9 cores come at the cost, morbidity, time, and complexity of an operation such as this performed under general anesthesia. So the real question remains whether HistoScanning or any emerging technology to image the prostate—improves visualization of prostate cancer. Although magnetic resonance imaging is beginning to show notable promise, the clinical value of most other modalities remains mostly anecdotal. As one whose desire for a solution remains frustratingly unfulfilled, I hope that some imaging technique will demonstrate clinical value during my career. J. Stephen Jones, M.D., Department of Regional Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio

REPLY

In accordance with your comprehensive notes, we have to search for diagnostic improvement and underline the need further investigations in the field of prostate cancer diagnostics and staging. Minimally invasive techniques, focal and targeted therapy modalities, and low-risk cancer surveillance probably are future treatment modalities for prostate malignancies that progressively challenge common diagnostic pathways. Sophisticated therapy strategies will require reliable staging results. The constant increase of cores taken during systematic prostate biopsy apparently will not overcome the well-known diagnostic uncertainties. Consequently, imaging techniques and methods of biopsy targeting will gain in importance. Clearly, the presented data do not show significant improvement in the overall detection rate of prostate cancer in our patient cohort. Further, the maximum number of 9 biopsy cores must be attributed to the initial study design and will undergo further investigation; however, the results rather support the study approach than reduce its validity. Considering the indeterminate number of cancers, the proof of superiority remains incomputable. Compared with the current standard of care of 12 to 14 cores, we detected no significant limitations, although perineal-targeted biopsies took significantly fewer cores (3-9 cores [35%]). Maintaining the detection rate unchanged and focusing on 1 to 3 preselected suspicious index lesions display a proof of principle rather than disappointing results. In line with future treatment options mentioned above, any less invasive, focused diagnostic procedure represents an encouraging advance compared with the common and recommended practice of a nonselective, systematic biopsy of the prostate to harbor cancerous tissue. Moritz F. Hamann, M.D., Department of Urology and Pediatric Urology, University of SchleswigeHolstein, Campus Kiel, Kiel, Germany

As mentioned by the authors, further improvement of the outcome of HistoScanning-based targeted biopsies of prostate is expected when an implementation of image-fusion application between the “off-line” generated 3D tumor map and the real-time ultrasound guiding the needle will be available; similar to the results presented already when using ultrasound-MRI image fusion applications for prostate biopsy. Of course, the ultimate biopsy workflow (which I am currently engaged in developing) that urologist are asking for is the one comprised of real-time ultrasound-based tissue characterization and real-time ultrasound guidance of the needle to the lesion.

References

1. Heidenreich A, Bellmunt J, Bolla M, et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011;59:61-71.

2. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Prostate Cancer Early Detection. Available at http://www.nccn.org 2011 Accessed May 2011.

3. Abdollah F, Novara G, Briganti A, et al. Trans-rectal versus transperineal saturation re-biopsy of the prostate: is there a difference in cancer detection rate? Urology. 2011;77:921-925.

4. Hara R, Yoshimasa J, Tomohiro F, et al. Optimal approach for prostate cancer detection as initial biopsy: prospective randomized study comparing transperineal versus transrectal systematic 12-core biopsy. Urology. 2008;71:191-195.

5. Patel AR, Jones JS. Optimal biopsy strategies for the diagnosis and staging of prostate cancer. Curr Opin Urol. 2009;19:232-237.

6. Al Otaibi M, Ross P, Fahmy N, et al. Role of repeated biopsy of the prostate in predicting disease progression in patients with prostate cancer on active surveillance. Cancer. 2008;113:286-292.

7. Braeckman J, Autier P, Garbar C, et al. Computer-aided ultrasonography (HistoScanning): a novel technology for locating and characterizing prostate cancer. BJU Int. 2008;101:293-298.

8. Braeckman J, Autier P, Soviany C, et al. The accuracy of transrectal ultrasonography supplemented with computer-aided ultrasonography for detecting small prostate cancers. BJU Int. 2008;102:1560-1565.

9. Presti JC Jr, O’Dowd G, Miller C, et al. Extended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: results of a community multi-practice study. J Urol. 2003;169:125-129.

10. Turkbey B, Mani H, Shah V, et al. Multiparametric 3T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. J Urol. 2011;186: 1818-1824.

11. Trabulsi EJ, Sackett D, Gomella L, et al. Enhanced transrectal ultrasound modalities in the diagnosis of prostate cancer. Urology. 2010;76:1025-1033.

12. Simmons LA, Autier P, Zat_ura F, et al. Detection, localisation and characterisation of prostate cancer by Prostate HistoScanning. BJU Int. 2012;110:28-35.

13. Emiliozzi P, Corsetti A, Tassi B, et al. Best approach for prostate cancer detection: a prospective study on transperineal versus transrectal six-core prostate biopsy. Urology. 2003;61:961-966.

14. Taira AV, Merrick GS, Galbreath RW, et al. Performance of transperineal template-guided mapping biopsy in detecting prostate cancer in the initial and repeat biopsy setting. Prostate Cancer Prostatic Dis. 2010;13:71-77.

 

Other research papers related to the management of Prostate cancer were published on this Scientific Web site:

Prostate Cancer: Androgen-driven “Pathomechanism” in Early-onset Forms of the Disease

Prostate Cancer and Nanotecnology

Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition

Imaging agent to detect Prostate cancer-now a reality

Scientists use natural agents for prostate cancer bone metastasis treatment

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?

Imaging agent to detect Prostate cancer-now a reality

Scientists use natural agents for prostate cancer bone metastasis treatment

Today’s fundamental challenge in Prostate cancer screening

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

Men With Prostate Cancer More Likely to Die from Other Causes

New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

New clinical results supports Imaging-guidance for targeted prostate biopsy

 

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The unfortunate ending of the Tower of Babel construction project and its effect on modern imaging-based cancer patients’ management


The story of the city of Babel is recorded in the book of Genesis 11 1-9. At that time, everyone on earth spoke the same language.

Picture: Pieter Bruegel the Elder: The Tower of Babel_(Vienna)

It is probably safe to assume that medical practitioners at that time were reporting the status of their patients in a standard manner. Although not mentioned, one might imagine that, at that time, ultrasound or MRI scans were also reported in a standard and transferrable manner. The people of Babel noticed the potential in uniform communication and tried to build a tower so high that it would  reach the gods. Unfortunately, God did not like that, so he went down (in person) and confounded people’s speech, so that they could not understand each another. Genesis 11:7–8.

This must be the explanation for our inability to come to a consensus on reporting of patients’ imaging-outcome. Progress in development of efficient imaging protocols and in clinical management of patients is withheld due to high variability and subjectivity of clinicians’ approach to this issue.

Clearly, a justification could be found for not reaching a consensus on imaging protocols: since the way imaging is performed affects the outcome, (i.e. the image and its interpretation) it takes a long process of trial-and-error to come up with the best protocol.  But, one might wonder, wouldn’t the search for the ultimate protocol converge faster if all practitioners around the world, who are conducting hundreds of clinical studies related to imaging-based management of cancer patients, report their results in a standardized and comparable manner?

Is there a reason for not reaching a consensus on imaging reporting? And I’m not referring only to intra-modality consensus, e.g. standardizing all MRI reports. I’m referring also to inter-modality consensus to enable comparison and matching of reports generated from scans of the same organ by different modalities, e.g. MRI, CT and ultrasound.

As developer of new imaging-based technologies, my personal contribution to promoting standardized and objective reporting was the implementation of preset reporting as part of the prostate-HistoScanning product design. For use-cases, as demonstrated below, in which prostate cancer patients were also scanned by MRI a dedicated reporting scheme enabled matching of the HistoScanning scan results with the prostate’s MRI results.

The MRI reporting scheme used as a reference is one of the schemes offered in a report by Miss Louise Dickinson on the following European consensus meeting : Magnetic Resonance Imaging for the Detection, Localisation, and Characterisation of Prostate Cancer: Recommendations from a European Consensus Meeting, Louise Dickinson a,b,c,*, Hashim U. Ahmed a,b, Clare Allen d, Jelle O. Barentsz e, Brendan Careyf, Jurgen J. Futterer e, Stijn W. Heijmink e, Peter J. Hoskin g, Alex Kirkham d, Anwar R. Padhani h, Raj Persad i, Philippe Puech j, Shonit Punwani d, Aslam S. Sohaib k, Bertrand Tomball,Arnauld Villers m, Jan van der Meulen c,n, Mark Emberton a,b,c,

http://www.europeanurology.com/article/S0302-2838(10)01187-5

Image of MRI reporting scheme taken from the report by Miss Louise Dickinson

The corresponding HistoScanning report is following the same prostate segmentation and the same analysis plans:


Preset reporting enabling matching of HistoScanning and MRI reporting of the same case.

It is my wish that already in the near-future, the main radiology societies (RSNA, ESR, etc..) will join together to build the clinical Imaging’s “Tower of Babel” to effectively address the issue of standardizing reporting of imaging procedures. This time it will not be destroyed…:-)

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Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-guided intervention?


Knowing the tumor’s size and location, could we target treatment to THE ROI by applying imaging-guided intervention?

Author: Dror Nir, PhD

 

Advances in techniques for cancer lesions’ detection and localisation [1-6] opened the road to methods of localised (“focused”) cancer treatment [7-10].  An obvious challenge on the road is reassuring that the imaging-guided treatment device indeed treats the region of interest and preferably, only it.

A step in that direction was taken by a group of investigators from Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada who evaluate the feasibility and safety of magnetic resonance (MR) imaging–controlled transurethral ultrasound therapy for prostate cancer in humans [7]. Their study’s objective was to prove that using real-time MRI guidance of HIFU treatment is possible and it guarantees that the location of ablated tissue indeed corresponds to the locations planned for treatment. Eight eligible patients were recruited.

 

The setup

 

Treatment protocol

 

The result

 

“There was excellent agreement between the zone targeted for treatment and the zone of thermal injury, with a targeting accuracy of ±2.6 mm. In addition, the temporal evolution of heating was very consistent across all patients, in part because of the ability of the system to adapt to changes in perfusion or absorption properties according to the temperature measurements along the target boundary.”

 

Technological problems to be resolved in the future:

“Future device designs could incorporate urinary drainage during the procedure, given the accumulation of urine in the bladder during treatment.”

“Sufficient temperature resolution could be achieved only by using 10-mm-thick sections. Our numeric studies suggest that 5-mm-thick sections are necessary for optimal three-dimensional conformal heating and are achievable by using endorectal imaging coils or by performing the treatment with a 3.0-T platform.”

Major limitation: “One of the limitations of the study was the inability to evaluate the efficacy of this treatment; however, because this represents, to our knowledge, the first use of this technology in human prostate, feasibility and safety were emphasized. In addition, the ability to target the entire prostate gland was not assessed, again for safety considerations. We have not attempted to evaluate the effectiveness of this treatment for eradicating cancer or achieving durable biochemical non-evidence of disease status.”

References

  1. SIMMONS (L.A.M.), AUTIER (P.), ZATURA (F.), BRAECKMAN (J.G.), PELTIER (A.), ROMICS (I.), STENZL (A.), TREURNICHT (K.), WALKER (T.), NIR (D.), MOORE (C.M.), EMBERTON (M.). Detection, localisation and characterisation of prostate cancer by Prostate HistoScanning.. British Journal of Urology International (BJUI). Issue 1 (July). Vol. 110, Page(s): 28-35
  2. WILKINSON (L.S.), COLEMAN (C.), SKIPPAGE (P.), GIVEN-WILSON (R.), THOMAS (V.). Breast HistoScanning: The development of a novel technique to improve tissue characterization during breast ultrasound. European Congress of Radiology (ECR), A.4030, C-0596, 03-07/03/2011.
  3. Hebert Alberto Vargas, MD, Tobias Franiel, MD,Yousef Mazaheri, PhD, Junting Zheng, MS, Chaya Moskowitz, PhD, Kazuma Udo, MD, James Eastham, MD and Hedvig Hricak, MD, PhD, Dr(hc) Diffusion-weighted Endorectal MR Imaging at 3 T for Prostate Cancer: Tumor Detection and Assessment of Aggressiveness. June 2011 Radiology, 259,775-784.
  4. Wendie A. Berg, Kathleen S. Madsen, Kathy Schilling, Marie Tartar, Etta D. Pisano, Linda Hovanessian Larsen, Deepa Narayanan, Al Ozonoff, Joel P. Miller, and Judith E. Kalinyak Breast Cancer: Comparative Effectiveness of Positron Emission Mammography and MR Imaging in Presurgical Planning for the Ipsilateral Breast Radiology January 2011 258:1 59-72.
  5. Anwar R. Padhani, Dow-Mu Koh, and David J. Collins Reviews and Commentary – State of the Art: Whole-Body Diffusion-weighted MR Imaging in Cancer: Current Status and Research Directions Radiology December 2011 261:3 700-718
  6. Eggener S, Salomon G, Scardino PT, De la Rosette J, Polascik TJ, Brewster S. Focal therapy for prostate cancer: possibilities and limitations. Eur Urol 2010;58(1):57–64).
  7. Rajiv Chopra, PhD, Alexandra Colquhoun, MD, Mathieu Burtnyk, PhD, William A. N’djin, PhD, Ilya Kobelevskiy, MSc, Aaron Boyes, BSc, Kashif Siddiqui, MD, Harry Foster, MD, Linda Sugar, MD, Masoom A. Haider, MD, Michael Bronskill, PhD and Laurence Klotz, MD. MR Imaging–controlled Transurethral Ultrasound Therapy for Conformal Treatment of Prostate Tissue: Initial Feasibility in Humans. October 2012 Radiology, 265,303-313.
  8. Black, Peter McL. M.D., Ph.D.; Alexander, Eben III M.D.; Martin, Claudia M.D.; Moriarty, Thomas M.D., Ph.D.; Nabavi, Arya M.D.; Wong, Terence Z. M.D., Ph.D.; Schwartz, Richard B. M.D., Ph.D.; Jolesz, Ferenc M.D.  Craniotomy for Tumor Treatment in an Intraoperative Magnetic Resonance Imaging Unit. Neurosurgery: September 1999 – Volume 45 – Issue 3 – p 423
  9. Medel, Ricky MD,  Monteith, Stephen J. MD, Elias, W. Jeffrey MD, Eames, Matthew PhD, Snell, John PhD, Sheehan, Jason P. MD, PhD, Wintermark, Max MD, MAS, Jolesz, Ferenc A. MD, Kassell, Neal F. MD. Neurosurgery: Magnetic Resonance–Guided Focused Ultrasound Surgery: Part 2: A Review of Current and Future Applications. October 2012 – Volume 71 – Issue 4 – p 755–763
  10. Bruno Quesson PhD, Jacco A. de Zwart PhD, Chrit T.W. Moonen PhD. Magnetic resonance temperature imaging for guidance of thermotherapy. Journal of Magnetic Resonance Imaging, Special Issue: Interventional MRI, Part 1, Volume 12, Issue 4, pages 525–533, October 2000

Writer: Dror Nir, PhD

 

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Author and Curator: Dror Nir, PhD

Radiology congresses are all about imaging in medicine. Interestingly, radiology originates from radiation. It was the discovery of X-ray radiation at the beginning of the 20th century that opened the road to “seeing” the inside of the human body without harming it (at that time that meant cutting into the body).

Radiology meetings are about sharing experience and knowhow on imaging-based management patients. The main topic is always image-interpretation: the bottom line of clinical radiology! This year’s European Congress of Radiology (ECR) dedicated few of its sessions to recent developments in image-interpretation tools. I chose to discuss the one that I consider contributing the most to the future of cancer patients’ management.

In the refresher course dedicated to computer application the discussion was aimed at understanding the question “How do image processing and CAD impact radiological daily practice?” Experts’ reviews gave the audience some background information on the following subjects:

  1. A.     The link between image reconstruction and image analysis.
  2. B.     Semantic web technologies for sharing and reusing imaging-related information
  3. C.     Image processing and CAD: workflow in clinical practice.

I find item A to be a fundamental education item. Not once did I hear a radiologist saying: “I know this is the lesion because it’s different on the image”.  Being aware of the computational concepts behind image rendering, even if it is at a very high level and lacking deep understanding of the computational processes,  will contribute to more balanced interpretations.

Item B is addressing the dream of investigators worldwide. Imagine that we could perform a web search and find educating, curated materials linking visuals and related clinical information, including standardized pathology reporting. We would only need to remember that search engines used certain search methods and agree, worldwide, on the method and language to be used when describing things. Having such tools is a pre-requisite to successful pharmaceutical and bio-tech development.

I find item C strongly linked to A, as all methods for better image interpretation must fit into a workflow. This is a design goal that is not trivial to achieve. To understand what I mean by that, try to think about how you could integrate the following examples in your daily workflow: i.e. what kind of expertise is needed for execution, how much time it will take, do you have the infrastructure?

In the rest of this post, I would like to highlight, through examples that were discussed during ECR 2012, the aspect of improving cancer patients’ clinical assessment by using information fusion to support better image interpretation.

  • Adding up quantitative information from MR spectroscopy (quantifies biochemical property of a target lesion) and Dynamic Contrast Enhanced MR imaging (highlights lesion vasculature).

Image provided by: Dr. Pascal Baltzer, director of mammography at the centre for radiology at Friedrich Schiller University in Jena, Germany

  • Registration of images generated by different imaging modalities (Multi-modal imaging registration).

The following examples: Fig 2 demonstrates registration of a mammography image of a breast lesion to an MRI image of this lesion. Fig3 demonstrates registration of an ultrasound image of a breast lesion scanned by an Automatic Breast Ultrasound (ABUS) system and an MRI image of the same lesion.

Images provided by members of the HAMAM project (an EU, FP7 funded research project: Highly Accurate Breast Cancer Diagnosis through Integration of Biological Knowledge, Novel Imaging Modalities, and Modelling): http://www.hamam-project.org

 

 Multi-modality image registration is usually based on the alignment of image-features apparent in the scanned regions. For ABUS-MRI matching these were: the location of the nipple and the breast thickness; the posterior of the nipple in both modalities; the medial-lateral distance of the nipple to the breast edge on ultrasound; and an approximation of the rib­cage using a cylinder on the MRI. A mean accuracy of 14mm was achieved.

Also from the HAMAM project, registration of ABUS image to a mammography image:

registration of ABUS image to a mammography image, Image provided by members of the HAMAM project (an EU, FP7 funded research project: Highly Accurate Breast Cancer Diagnosis through Integration of Biological Knowledge, Novel Imaging Modalities, and Modelling): http://www.hamam-project.org

  • Automatic segmentation of suspicious regions of interest seen in breast MRI images

Segmentation of suspicious the lesions on the image is the preliminary step in tumor evaluation; e.g. finding its size and location. Since lesions have different signal/image character­istics to the rest of the breast tissue, it gives hope for the development of computerized segmentation techniques. If successful, such techniques bear the promise of enhancing standardization in the reporting of lesions size and location: Very important information for the success of the treatment step.

Roberta Fusco of the National Cancer Institute of Naples Pascal Foundation, Naples/IT suggested the following automatic method for suspi­cious ROI selection within the breast using dynamic-derived information from DCE-MRI data.

 

Automatic segmentation of suspicious ROI in breast MRI images, image provided by Roberta Fusco of the National Cancer Institute of Naples Pascal Foundation, Naples/IT

 

 Her algorithm includes three steps (Figure 2): (i) breast mask extraction by means of automatic intensity threshold estimation (Otsu Thresh-holding) on the par­ametric map obtained through the sum of intensity differences (SOD) calculated pixel by pixel; (ii) hole-filling and leakage repair by means of morphological operators: closing is required to fill the holes on the boundaries of breast mask, filling is required to fill the holes within the breasts, erosion is required to reduce the dilation obtained by the closing operation; (iii) suspicious ROIs extraction: a pixel is assigned to a suspicious ROI if it satisfies two conditions: the maximum of its normalized time-intensity curve should be greater than 0.3 and the maximum signal intensity should be reached before the end of the scan time. The first condition assures that the pixels within the ROI have a significant contrast agent uptake (thus excluding type I and type II curves) and the second condition is required for the time-intensity pattern to be of type IV or V (thus excluding type III curves).

Written by: Dror Nir, PhD

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Author: Dror Nir, PhD

 

The most stressful period in a cancer patients’ pathway is from the moment they fail a screening test or present with suspicious symptoms to the moment they are diagnosed. Today’s medical guidelines require histopathology findings as the only acceptable proof: positive results  mean you are a cancer patient, negative results mean, well…maybe you are and maybe you are not. You now enter into what might be a very long period, sometime years, of uncertainty regarding your health and prospects. And why?

Because the substance for histopathology is acquired by biopsies, and biopsies are known to be inaccurate. For example, breast and prostate biopsies  fail to find 25% to 35% of the cancer lesions at the first biopsy session.

Therefore, it is not surprising that from the beginning of this procedure,  medical practitioners look for ways to incorporate imaging into the workflow. In the last decade, significant progress has been made in the introduction of imaging-guided biopsies. The most common modalities were ultrasound and CT/mammography. Recently, as the industry solved the issues of magnetic field compatibility for biopsy needles and the introduction of open MRI systems, MRI-guided biopsies were also made  possible.

Ultrasound-guided biopsies are  by far the most commonly used procedure. Why? Because they  can be often performed as an office-based procedure. Here are some interesting links to YouTube videos describing such procedures:

  • Prostate

Prostate Ultrasound and Prostate Biopsy by Dr. Neil Baum

Transrectal ultrasound (Trus) Biopsy of the prostate

  • Breast

Ultrasound-Guided Breast Biopsy

Breast Tissue Biopsy

The main advantages: they are easily accessible, low cost and quick. The disadvantages of these procedures are  that they are very much operator dependent, rather than standardized, and there are no quality assurance guidelines attached. Efforts to standardize ultrasound-based biopsies and increase their efficiency are evident by recent introductions of ultrasound systems into the market ,  which support real-time guided biopsies and ultrasound applications that perform real-time biopsy tracking. But these systems are still far from being widely available. I will touch on this issue in my upcoming posts as I am part of these efforts.

CT and Mammography guided biopsies require more sophisticated equipment and well-trained operators. As an example:

Breast Biopsy – What To Expect

The main advantage: if you return to the same operator, the process is likely to be reproducible. The disadvantages are identical to that of ultrasound-based biopsies. It is worthwhile to note that, recently, radiologists who perform biopsies are required to go through a certification process. Still, such certification demands vary between the various radiology societies.

MRI-guided biopsies are an even more sophisticate and complex procedure:

  • Prostate:

DynaTRIM Video

DynaTRIM Intervention

An interesting quote from Dr. Hashim U. Ahmed, M.D., MRCS, Division of Urology  Department of Surgery, University College of London (https://mail.google.com/mail/u/1/?shva=1#label/Work%2FLinks%2FAuntMinnie/139d9c5bc6bda842): “Advocating the widespread use of MRI before biopsy in a population of men with risk parameters for harboring prostate cancer has a number of advantages, which might ultimately benefit the care these men undergo. Increasing the detection of prostate cancer that requires treatment while avoiding biopsy – and hence unnecessary treatment – in those with insignificant or no cancer are compelling arguments for this approach.”

  • Breast

MRI Breast Biopsy – Diagnostic and Biopsy Services for Breast Evaluation

I recommend reading the following article regarding the use of Open MRI to guide freehand biopsies of breast lesions. Especially interesting is the discussion where the authors give a good description of the difficulties in breast biopsies they are trying to overcome in order to achieve good lesion sampling.

MR-guided Freehand Biopsy of Breast Lesions in a 1.0-T Open MR Imager with a Near-Real-time Interactive Platform: Preliminary Experience Frank Fischbach, MD, et. al

http://radiology.rsna.org/content/early/2012/08/14/radiol.12110981.full?sid=bd45ceb4-9c8d-4ffc-b80b-0345ee679b4e

The question remains: which biopsy procedure is the best? And does this question have one coherent answer, i.e. one that will satisfy the patients, the doctors and the health-care insurers?  Will the answer to this question remain the subject of endless uncoordinated clinical studies?

If anyone who reads this post knows on methodological scientific or regulatory initiatives aimed at answering this question on a level of global guide lines  I would appreciate his comment.

Written by: Dror Nir, PhD.

 

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