title: Magnetic resonance imaging-targeted, 3D transrectal ultrasound-guided fusion biopsy for prostate cancer: Quantifying the impact of needle delivery error on diagnosis.
abstract: OBJECTIVE
  Magnetic resonance imaging (MRI)-targeted, 3D transrectal ultrasound (TRUS)-guided "fusion" prostate biopsy intends to reduce the ∼23% false negative rate of clinical two-dimensional TRUS-guided sextant biopsy. Although it has been reported to double the positive yield, MRI-targeted biopsies continue to yield false negatives. Therefore, the authors propose to investigate how biopsy system needle delivery error affects the probability of sampling each tumor, by accounting for uncertainties due to guidance system error, image registration error, and irregular tumor shapes.
  
  
  METHODS
  T2-weighted, dynamic contrast-enhanced T1-weighted, and diffusion-weighted prostate MRI and 3D TRUS images were obtained from 49 patients. A radiologist and radiology resident contoured 81 suspicious regions, yielding 3D tumor surfaces that were registered to the 3D TRUS images using an iterative closest point prostate surface-based method to yield 3D binary images of the suspicious regions in the TRUS context. The probabilityP of obtaining a sample of tumor tissue in one biopsy core was calculated by integrating a 3D Gaussian distribution over each suspicious region domain. Next, the authors performed an exhaustive search to determine the maximum root mean squared error (RMSE, in mm) of a biopsy system that gives P ≥ 95% for each tumor sample, and then repeated this procedure for equal-volume spheres corresponding to each tumor sample. Finally, the authors investigated the effect of probe-axis-direction error on measured tumor burden by studying the relationship between the error and estimated percentage of core involvement.
  
  
  RESULTS
  Given a 3.5 mm RMSE for contemporary fusion biopsy systems,P ≥ 95% for 21 out of 81 tumors. The authors determined that for a biopsy system with 3.5 mm RMSE, one cannot expect to sample tumors of approximately 1 cm(3) or smaller with 95% probability with only one biopsy core. The predicted maximum RMSE giving P ≥ 95% for each tumor was consistently greater when using spherical tumor shapes as opposed to no shape assumption. However, an assumption of spherical tumor shape for RMSE = 3.5 mm led to a mean overestimation of tumor sampling probabilities of 3%, implying that assuming spherical tumor shape may be reasonable for many prostate tumors. The authors also determined that a biopsy system would need to have a RMS needle delivery error of no more than 1.6 mm in order to sample 95% of tumors with one core. The authors' experiments also indicated that the effect of axial-direction error on the measured tumor burden was mitigated by the 18 mm core length at 3.5 mm RMSE.
  
  
  CONCLUSIONS
  For biopsy systems with RMSE ≥ 3.5 mm, more than one biopsy core must be taken from the majority of tumors to achieveP ≥ 95%. These observations support the authors' perspective that some tumors of clinically significant sizes may require more than one biopsy attempt in order to be sampled during the first biopsy session. This motivates the authors' ongoing development of an approach to optimize biopsy plans with the aim of achieving a desired probability of obtaining a sample from each tumor, while minimizing the number of biopsies. Optimized planning of within-tumor targets for MRI-3D TRUS fusion biopsy could support earlier diagnosis of prostate cancer while it remains localized to the gland and curable.
authors.affiliation: Department of Medical Biophysics, The University of Western Ontario, London, Ontario N6A 3K7, Canada.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Martin
authors.affiliation: Department of Medical Imaging, The University of Western Ontario, London, Ontario N6A 3K7, Canada and Robarts Research Institute, The University of Western Ontario, London, Ontario N6A 3K7, Canada.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Cool
authors.affiliation: Department of Medical Imaging, The University of Western Ontario, London, Ontario N6A 3K7, Canada.
authors.forename: Cesare
authors.initials: C
authors.lastname: Romagnoli
authors.affiliation: Department of Medical Biophysics, The University of Western Ontario, London, Ontario N6A 3K7, Canada; Department of Medical Imaging, The University of Western Ontario, London, Ontario N6A 3K7, Canada; and Robarts Research Institute, The University of Western Ontario, London, Ontario N6A 3K7, Canada.
authors.forename: Aaron
authors.initials: A
authors.lastname: Fenster
authors.affiliation: Department of Medical Biophysics, The University of Western Ontario, London, Ontario N6A 3K7, Canada and Department of Oncology, The University of Western Ontario, London, Ontario N6A 3K7, Canada.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Ward
mesh_terms: D001707:Biopsy, Needle / Q000379:methods*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005188:False Negative Reactions; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D061705:Image-Guided Biopsy / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016011:Normal Distribution; D011336:Probability; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D012007:Rectum / Q000000981:diagnostic imaging; D012189:Retrospective Studies; D047368:Tumor Burden; D014463:Ultrasonography; D035501:Uncertainty