Cesare Romagnoli

Mechanically assisted 3D ultrasound guided prostate biopsy system

There are currently limitations associated with the prostate biopsy procedure, which is the most commonly used method for a definitive diagnosis of prostate cancer. With the use of two-dimensional (2D) transrectal ultrasound (TRUS) for needle-guidance in this procedure, the physician has restricted anatomical reference points for guiding the needle to target sites. Further, any motion of the physicians hand during the procedure may cause the prostate to move or deform to a prohibitive extent. These variations make it difficult to establish a consistent reference frame for guiding a needle. We have developed a 3D navigation system for prostate biopsy, which addresses these shortcomings. This system is composed of a 3D US imaging subsystem and a passive mechanical arm to minimize prostate motion. To validate our prototype, a series of experiments were performed on prostate phantoms. The 3D scan of the string phantom produced minimal geometric distortions, and the geometric error of the 3D imaging subsystem was 0.37 mm. The accuracy of 3D prostate segmentation was determined by comparing the known volume in a certified phantom to a reconstructed volume generated by our system and was shown to estimate the volume with less then 5% error. Biopsy needle guidance accuracy tests in agar prostate phantoms showed that the mean error was 2.1 mm and the 3D location of the biopsy core was recorded with a mean error of 1.8 mm. In this paper, we describe the mechanical design and validation of the prototype system using an in vitro prostate phantom. Preliminary results from an ongoing clinical trial show that prostate motion is small with an in-plane displacement of less than 1 mm during the biopsy procedure.

Assessment of image registration accuracy in three-dimensional transrectal ultrasound guided prostate biopsy

PURPOSE Prostate biopsy, performed using two-dimensional (2D) transrectal ultrasound (TRUS) guidance, is the clinical standard for a definitive diagnosis of prostate cancer. Histological analysis of the biopsies can reveal cancerous, noncancerous, or suspicious, possibly precancerous, tissue. During subsequent biopsy sessions, noncancerous regions should be avoided, and suspicious regions should be precisely rebiopsied, requiring accurate needle guidance. It is challenging to precisely guide a needle using 2D TRUS due to the limited anatomic information provided, and a three-dimensional (3D) record of biopsy locations for use in subsequent biopsy procedures cannot be collected. Our tracked, 3D TRUS-guided prostate biopsy system provides additional anatomic context and permits a 3D record of biopsies. However, targets determined based on a previous biopsy procedure must be transformed during the procedure to compensate for intraprocedure prostate shifting due to patient motion and prostate deformation due to transducer probe pressure. Thus, registration is a critically important step required to determine these transformations so that correspondence is maintained between the prebiopsied image and the real-time image. Registration must not only be performed accurately, but also quickly, since correction for prostate motion and deformation must be carried out during the biopsy procedure. The authors evaluated the accuracy, variability, and speed of several surface-based and image-based intrasession 3D-to-3D TRUS image registration techniques, for both rigid and nonrigid cases, to find the required transformations. METHODS Our surface-based rigid and nonrigid registrations of the prostate were performed using the iterative-closest-point algorithm and a thin-plate spline algorithm, respectively. For image-based rigid registration, the authors used a block matching approach, and for nonrigid registration, the authors define the moving image deformation using a regular, 3D grid of B-spline control points. The authors measured the target registration error (TRE) as the postregistration misalignment of 60 manually marked, corresponding intrinsic fiducials. The authors also measured the fiducial localization error (FLE), the effect of segmentation variability, and the effect of fiducial distance from the transducer probe tip. Lastly, the authors performed 3D principal component analysis (PCA) on the x, y, and z components of the TREs to examine the 95% confidence ellipsoids describing the errors for each registration method. RESULTS Using surface-based registration, the authors found mean TREs of 2.13 +/- 0.80 and 2.09 +/- 0.77 mm for rigid and nonrigid techniques, respectively. Using image-based rigid and non-rigid registration, the authors found mean TREs of 1.74 +/- 0.84 and 1.50 +/- 0.83 mm, respectively. Our FLE was 0.21 mm and did not dominate the overall TRE. However, segmentation variability contributed substantially approximately50%) to the TRE of the surface-based techniques. PCA showed that the 95% confidence ellipsoid encompassing fiducial distances between the source and target registra- tion images was reduced from 3.05 to 0.14 cm3, and 0.05 cm3 for the surface-based and image-based techniques, respectively. The run times for both registration methods were comparable at less than 60 s. CONCLUSIONS Our results compare favorably with a clinical need for a TRE of less than 2.5 mm, and suggest that image-based registration is superior to surface-based registration for 3D TRUS-guided prostate biopsies, since it does not require segmentation.

Prostate: Registration of Digital Histopathologic Images to in Vivo MR Images Acquired by Using Endorectal Receive Coil

PURPOSE To develop and evaluate a technique for the registration of in vivo prostate magnetic resonance (MR) images to digital histopathologic images by using image-guided specimen slicing based on strand-shaped fiducial markers relating specimen imaging to histopathologic examination. MATERIALS AND METHODS The study was approved by the institutional review board (the University of Western Ontario Health Sciences Research Ethics Board, London, Ontario, Canada), and written informed consent was obtained from all patients. This work proposed and evaluated a technique utilizing developed fiducial markers and real-time three-dimensional visualization in support of image guidance for ex vivo prostate specimen slicing parallel to the MR imaging planes prior to digitization, simplifying the registration process. Means, standard deviations, root-mean-square errors, and 95% confidence intervals are reported for all evaluated measurements. RESULTS The slicing error was within the 2.2 mm thickness of the diagnostic-quality MR imaging sections, with a tissue block thickness standard deviation of 0.2 mm. Rigid registration provided negligible postregistration overlap of the smallest clinically important tumors (0.2 cm(3)) at histologic examination and MR imaging, whereas the tested nonrigid registration method yielded a mean target registration error of 1.1 mm and provided useful coregistration of such tumors. CONCLUSION This method for the registration of prostate digital histopathologic images to in vivo MR images acquired by using an endorectal receive coil was sufficiently accurate for coregistering the smallest clinically important lesions with 95% confidence.

Evaluation of MRI-TRUS Fusion Versus Cognitive Registration Accuracy for MRI-Targeted, TRUS-Guided Prostate Biopsy

OBJECTIVE The purpose of this article is to compare transrectal ultrasound (TRUS) biopsy accuracies of operators with different levels of prostate MRI experience using cognitive registration versus MRI-TRUS fusion to assess the preferred method of TRUS prostate biopsy for MRI-identified lesions. SUBJECTS AND METHODS; One hundred patients from a prospective prostate MRI-TRUS fusion biopsy study were reviewed to identify all patients with clinically significant prostate adenocarcinoma (PCA) detected on MRI-targeted biopsy. Twenty-five PCA tumors were incorporated into a validated TRUS prostate biopsy simulator. Three prostate biopsy experts, each with different levels of experience in prostate MRI and MRI-TRUS fusion biopsy, performed a total of 225 simulated targeted biopsies on the MRI lesions as well as regional biopsy targets. Simulated biopsies performed using cognitive registration with 2D TRUS and 3D TRUS were compared with biopsies performed under MRI-TRUS fusion. RESULTS Two-dimensional and 3D TRUS sampled only 48% and 45% of clinically significant PCA MRI lesions, respectively, compared with 100% with MRI-TRUS fusion. Lesion sampling accuracy did not statistically significantly vary according to operator experience or tumor volume. MRI-TRUS fusion-naïve operators showed consistent errors in targeting of the apex, midgland, and anterior targets, suggesting that there is biased error in cognitive registration. The MRI-TRUS fusion expert correctly targeted the prostate apex; however, his midgland and anterior mistargeting was similar to that of the less-experienced operators. CONCLUSION MRI-targeted TRUS-guided prostate biopsy using cognitive registration appears to be inferior to MRI-TRUS fusion, with fewer than 50% of clinically significant PCA lesions successfully sampled. No statistically significant difference in biopsy accuracy was seen according to operator experience with prostate MRI or MRI-TRUS fusion.

2D-3D rigid registration to compensate for prostate motion during 3D TRUS-guided biopsy.

PURPOSE Three-dimensional (3D) transrectal ultrasound (TRUS)-guided systems have been developed to improve targeting accuracy during prostate biopsy. However, prostate motion during the procedure is a potential source of error that can cause target misalignments. The authors present an image-based registration technique to compensate for prostate motion by registering the live two-dimensional (2D) TRUS images acquired during the biopsy procedure to a preacquired 3D TRUS image. The registration must be performed both accurately and quickly in order to be useful during the clinical procedure. METHODS The authors implemented an intensity-based 2D-3D rigid registration algorithm optimizing the normalized cross-correlation (NCC) metric using Powells method. The 2D TRUS images acquired during the procedure prior to biopsy gun firing were registered to the baseline 3D TRUS image acquired at the beginning of the procedure. The accuracy was measured by calculating the target registration error (TRE) using manually identified fiducials within the prostate; these fiducials were used for validation only and were not provided as inputs to the registration algorithm. They also evaluated the accuracy when the registrations were performed continuously throughout the biopsy by acquiring and registering live 2D TRUS images every second. This measured the improvement in accuracy resulting from performing the registration, continuously compensating for motion during the procedure. To further validate the method using a more challenging data set, registrations were performed using 3D TRUS images acquired by intentionally exerting different levels of ultrasound probe pressures in order to measure the performance of our algorithm when the prostate tissue was intentionally deformed. In this data set, biopsy scenarios were simulated by extracting 2D frames from the 3D TRUS images and registering them to the baseline 3D image. A graphics processing unit (GPU)-based implementation was used to improve the registration speed. They also studied the correlation between NCC and TREs. RESULTS The root-mean-square (RMS) TRE of registrations performed prior to biopsy gun firing was found to be 1.87 ± 0.81 mm. This was an improvement over 4.75 ± 2.62 mm before registration. When the registrations were performed every second during the biopsy, the RMS TRE was reduced to 1.63 ± 0.51 mm. For 3D data sets acquired under different probe pressures, the RMS TRE was found to be 3.18 ± 1.6 mm. This was an improvement from 6.89 ± 4.1 mm before registration. With the GPU based implementation, the registrations were performed with a mean time of 1.1 s. The TRE showed a weak correlation with the similarity metric. However, the authors measured a generally convex shape of the metric around the ground truth, which may explain the rapid convergence of their algorithm to accurate results. CONCLUSIONS Registration to compensate for prostate motion during 3D TRUS-guided biopsy can be performed with a measured accuracy of less than 2 mm and a speed of 1.1 s, which is an important step toward improving the targeting accuracy of a 3D TRUS-guided biopsy system.

US-guided therapy of calcific tendinopathy: clinical and radiological outcome assessment in shoulder and non-shoulder tendons.

PURPOSE To analyze the effectiveness and complication rate of ultrasound (US)-guided perforation and lavage using a two-needle technique with 16 - 18 G needles in the treatment of patients with calcific tendinopathy in the shoulder, elbow, hip, and knee by radiological and clinical follow-up. MATERIALS AND METHODS A retrospective chart review was performed and 40 patients (13 male, 27 female; mean age, 53.5 years; range 24 -74 years) were identified as having received US-guided perforation and lavage due to symptomatic calcific tendinopathy of the rotator cuff tendons, triceps, extensor and flexor tendons at the elbow, rectus femoris tendon and patellar tendons. The radiographic outcome was assessed by comparison of the size and quality of the calcification before and 6 weeks after the procedure. On US images, the quality of the acoustic shadow was assessed, together with other alterations of the tendon and surrounding tissue. Patients were interviewed by telephone to assess the clinical outcome regarding pre-treatment and post-treatment pain and tendon function. RESULTS 34 shoulder tendons and 6 non-shoulder tendons were identified. The mean calcium reduction was 39.9 mm(2) (range, 0 - 215; p < 0.001), while 80 % of patient showed a resolution of more than 60 % resulting in good clinical improvement. A very low complication rate was found (1 partial tear). CONCLUSION The US-guided perforation and lavage technique is an effective and safe treatment for rotator cuff calcifications as well as for other body tendons. Although the two-needle technique and large needles were used in this study, a very low complication rate was detected.

Efficient Convex Optimization Approach to 3D Non-rigid MR-TRUS Registration

In this study, we propose an efficient non-rigid MR-TRUS deformable registration method to improve the accuracy of targeting suspicious locations during a 3D ultrasound (US) guided prostate biopsy. The proposed deformable registration approach employs the multi-channel modality independent neighbourhood descriptor (MIND) as the local similarity feature across the two modalities of MR and TRUS, and a novel and efficient duality-based convex optimization based algorithmic scheme is introduced to extract the deformations which align the two MIND descriptors. The registration accuracy was evaluated using 10 patient images by measuring the TRE of manually identified corresponding intrinsic fiducials in the whole gland and peripheral zone, and performance metrics (DSC, MAD and MAXD) for the apex, mid-gland and base of the prostate were also calculated by comparing two manually segmented prostate surfaces in the registered 3D MR and TRUS images. Experimental results show that the proposed method yielded an overall mean TRE of 1.74 mm, which is favorably comparable to a clinical requirement for an error of less than 2.5 mm.

Quantification of prostate deformation due to needle insertion during TRUS-guided biopsy: comparison of hand-held and mechanically stabilized systems.

PURPOSE Prostate biopsy is the clinical standard for the definitive diagnosis of prostate cancer. To overcome the limitations of 2D TRUS-guided biopsy systems when targeting preplanned locations, systems have been developed with 3D guidance to improve the accuracy of cancer detection. Prostate deformation due to needle insertion and biopsy gun firing is a potential source of error that can cause target misalignments during biopsies. METHODS The authors used nonrigid registration of 2D TRUS images to quantify the deformation that occurs during the needle insertion and the biopsy gun firing procedure and compare this effect in biopsies performed using a hand-held TRUS probe to those performed using a mechanically assisted 3D TRUS-guided biopsy system. The authors calculated a spatially varying 95% confidence interval on the prostate tissue motion and analyzed this motion both as a function of distance to the biopsy needle and as a function of distance to the lower piercing point of the prostate. The former is relevant because biopsy targets lie along the needle axis, and the latter is of particular importance due to the reported high concentration of prostate cancer in the peripheral zone, a substantial portion of which lies on the posterior side of the prostate where biopsy needles enter the prostate after penetrating the rectal wall during transrectal biopsy. RESULTS The results show that for both systems, the tissue deformation is such that throughout the length of the needle axis, including regions proximal to the lower piercing point, spherical tumors with a radius of 2.1 mm or more can be sampled with 95% confidence under the assumption of zero error elsewhere in the biopsy system. More deformation was observed in the direction orthogonal to the needle axis compared to the direction parallel to the needle axis; this is of particular importance given the long, narrow shape of the biopsy core. The authors measured lateral tissue motion proximal to the needle axis of not more than 1.5 mm, with 95% confidence. The authors observed a statistically significant and clinically insignificant maximum difference of 0.38 mm in the deformation, resulting from the hand-held and mechanically assisted systems along the needle axis, and the mechanical system resulted in a lower relative increase in deformation proximal to the needle axis during needle insertion, as well as lower variability of deformation during biopsy gun firing. CONCLUSIONS Given the clinical need to biopsy tumors of volume greater than or equal to 0.5 cm3, corresponding to spherical tumors with a radius of 5 mm or more, the tissue motion induced by needle insertion and gun firing is an important consideration when setting the design specifications for TRUS-guided prostate biopsy systems.

Evaluation of intersession 3D-TRUS to 3D-TRUS image registration for repeat prostate biopsies.

PURPOSE 3D-TRUS-guided prostate biopsy permits a 3D record of biopsy cores, supporting the planning of targets to resample or avoid during repeat biopsy sessions. Image registration is required in order to map biopsy targets planned on a previous sessions 3D-TRUS image into the context of the current session. The authors evaluated the performance of surface- and intensity-based rigid and nonrigid registration algorithms for this task using a clinically motivated success criterion of a maximum 2.5 mm target registration error (TRE). METHODS The authors collected two 3D-TRUS images for each of 13 patients, where each image was collected in a separate biopsy session, and the sessions were 1 week apart. The authors tested the iterative closest point and thin-plate spline surface-based registration methods, and the block matching and B-spline intensity-based methods. Manually marked intrinsic fiducials (calcifications) were used to calculate a TRE for each of the tested methods. In addition, error ellipsoids, anisotropy, and variability due to image segmentation were analyzed. All analysis was performed separately for the peripheral zone since this area harbors up to 80% of all prostate cancer. RESULTS Only the intensity-based nonrigid registration method met the success criterion for both the whole gland and the peripheral zone. Segmentation was a substantial contributor to registration error variability for the surface-based methods, and the surface-based methods resulted in greater error volumes and anisotropy. CONCLUSIONS Intensity-based rigid registration is clinically sufficient to register regions outside the peripheral zone, but nonrigid registration is required in order to register the peripheral zone with clinically needed accuracy. The clinical advantage of using nonrigid registration is questionable since the difference between the RMS TREs for rigid and nonrigid intensity-based registration could be considered to be small (0.3 mm) and is statistically significant. If the added clinical value in performing a nonrigid registration is insufficient given the additional time required for this computation, rigid registration alone may be suitable.

Magnetic Resonance Imaging–Guided Transurethral Ultrasound Ablation of Prostate Tissue in Patients with Localized Prostate Cancer: A Prospective Phase 1 Clinical Trial

BACKGROUND Magnetic resonance imaging-guided transurethral ultrasound ablation (MRI-TULSA) is a novel minimally invasive technology for ablating prostate tissue, potentially offering good disease control of localized cancer and low morbidity. OBJECTIVE To determine the clinical safety and feasibility of MRI-TULSA for whole-gland prostate ablation in a primary treatment setting of localized prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS A single-arm prospective phase 1 study was performed at three tertiary referral centers in Canada, Germany, and the United States. Thirty patients (median age: 69 yr; interquartile range [IQR]: 67-71 yr) with biopsy-proven low-risk (80%) and intermediate-risk (20%) PCa were treated and followed for 12 mo. INTERVENTION MRI-TULSA treatment was delivered with the therapeutic intent of conservative whole-gland ablation including 3-mm safety margins and 10% residual viable prostate expected around the capsule. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Primary end points were safety (adverse events) and feasibility (technical accuracy and precision of conformal thermal ablation). Exploratory outcomes included quality of life, prostate-specific antigen (PSA), and biopsy at 12 mo. RESULTS AND LIMITATIONS Median treatment time was 36min (IQR: 26-44) and prostate volume was 44ml (IQR: 38-48). Spatial control of thermal ablation was ±1.3mm on MRI thermometry. Common Terminology Criteria for Adverse Events included hematuria (43% grade [G] 1; 6.7% G2), urinary tract infections (33% G2), acute urinary retention (10% G1; 17% G2), and epididymitis (3.3% G3). There were no rectal injuries. Median pretreatment International Prostate Symptom Score 8 (IQR: 5-13) returned to 6 (IQR: 4-10) at 3 mo (mean change: -2; 95% confidence interval [CI], -4 to 1). Median pretreatment International Index of Erectile Function 13 (IQR: 6-28) recovered to 13 (IQR: 5-25) at 12 mo (mean change: -1; 95% CI, -5 to 3). Median PSA decreased 87% at 1 mo and was stable at 0.8 ng/ml (IQR: 0.6-1.1) to 12 mo. Positive biopsies showed 61% reduction in total cancer length, clinically significant disease in 9 of 29 patients (31%; 95% CI, 15-51), and any disease in 16 of 29 patients (55%; 95% CI, 36-74). CONCLUSIONS MRI-TULSA was feasible, safe, and technically precise for whole-gland prostate ablation in patients with localized PCa. Phase 1 data are sufficiently compelling to study MRI-TULSA further in a larger prospective trial with reduced safety margins. PATIENT SUMMARY We used magnetic resonance imaging-guided transurethral ultrasound to heat and ablate the prostate in men with prostate cancer. We showed that the treatment can be targeted within a narrow range (1mm) and has a well-tolerated side effect profile. A larger study is under way. TRIAL REGISTRATION NCT01686958, DRKS00005311.