Validation of a Novel Method of Measuring Cup Orientation Using BiPlanar Simultaneous Radiographic Images.

BACKGROUND: Accurate acetabular component positioning is paramount to the success of total hip arthroplasty (THA). Two-dimensional imaging alone remains a popular tool for implant position assessment despite known limitations. We investigated the accuracy of a novel method for assessing acetabular component position based upon orthogonal simultaneous biplanar X-ray images. METHODS: There were forty consecutive patients who had a preexisting THA on the contralateral side who underwent both computed tomography (CT) and simultaneous orthogonal biplanar radiographic scans for preoperative planning of THA. The operative inclination (OI) and operative anteversion (OA) of the acetabular cup were calculated by a new measurement method using the biplanar simultaneous scans. Those measurements were compared to measurement of the cup orientation on CT. The measurements were made by 2 independent observers. Interobserver correlation coefficients were calculated between the 2 observers to measure reliability. RESULTS: The mean error in OA measurement of the acetabular cup between simultaneous orthogonal biplanar radiographic and CT imaging was 0.5° (SD: 1.9°, minimum -4.0°, maximum 5.0°), the mean error in OI was 0.0° (SD: 1.7°, minimum -5.0°, maximum 4.0°). The average absolute error was 1.5° for OA and 1.2° for OI. Interobserver correlation coefficient was 0.83 for OA and 0.93 for OI. CONCLUSION: The novel method of measuring cup orientation using simultaneous biplanar radiographic scans utilized in this study was accurate and reproducible between observers compared to CT measurements.

The Safe Zone Range for Cup Anteversion Is Narrower Than for Inclination in THA.

BACKGROUND: Cup malposition is a common cause of impingement, limitation of ROM, acceleration of bearing wear, liner fracture, and instability in THA. Previous studies of the safe zone based on plain radiographs have limitations inherent to measuring angles from two-dimensional projections. The current study uses CT to measure component position in stable and unstable hips to assess the presence of a safe zone for cup position in THA. QUESTIONS/PURPOSES: (1) Does acetabular component orientation, when measured on CT, differ in stable components and those revised for recurrent instability? (2) Do CT data support historic safe zone definitions for component orientation in THA? METHODS: We identified 34 hips that had undergone revision of the acetabulum for recurrent instability that also had a CT scan of the pelvis between August 2003 and February 2017. We also identified 175 patients with stable hip replacements who also had a CT study for preoperative planning and intraoperative navigation of the contralateral side. For each CT study, one observer analyzed major factors including acetabular orientation, femoral anteversion, combined anteversion (the sum of femoral and anatomic anteversion), pelvic tilt, total offset difference, head diameter, age, sex, and body mass index. These measures were then compared among stable hips, hips with cup revision for anterior instability, and hips with cup revision for posterior instability. We used a clinically relevant measurement of operative anteversion and inclination as opposed to the historic use of radiographic anteversion and inclination. The percentage of unstable hips in the historic Lewinnek safe zone was calculated, and a new safe zone was proposed based on an area with no unstable hips. RESULTS: Anteriorly unstable hips compared with stable hips had higher operative anteversion of the cup (44° ± 12° versus 31° ± 11°, respectively; mean difference, 13°; 95% confidence interval [CI], 5°-21°; p = 0.003), tilt-adjusted operative anteversion of the cup (40° ± 6° versus 26° ± 10°, respectively; mean difference, 14°; 95% CI, 10°-18°; p < 0.001), and combined tilt-adjusted anteversion of the cup (64° ± 10° versus 54° ± 19°, respectively; mean difference, 10°; 95% CI, 1°-19°; p = 0.028). Posteriorly unstable hips compared with stable hips had lower operative anteversion of the cup (19° ± 15° versus 31° ± 11°, respectively; mean difference, -12°; 95% CI, -5° to -18°; p = 0.001), tilt-adjusted operative anteversion of the cup (19° ± 13° versus 26° ± 10°, respectively; mean difference, -8°; 95% CI, -14° to -2°; p = 0.014), pelvic tilt (0° ± 6° versus 4° ± 6°, respectively; mean difference, -4°; 95% CI, -7° to -1°; p = 0.007), and anatomic cup anteversion (25° ± 18° versus 34° ± 12°, respectively; mean difference, -9°; 95% CI, -1° to -17°; p = 0.033). Thirty-two percent of the unstable hips were located in the Lewinnek safe zone (11 of 34; 10 posterior dislocations, one anterior dislocation). In addition, a safe zone with no unstable hips was identified within 43° ± 12° of operative inclination and 31° ± 8° of tilt-adjusted operative anteversion. CONCLUSIONS: The current study supports the notion of a safe zone for acetabular component orientation based on CT. However, the results demonstrate that the historic Lewinnek safe zone is not a reliable predictor of future stability. Analysis of tilt-adjusted operative anteversion and operative inclination demonstrates a new safe zone where no hips were revised for recurrent instability that is narrower for tilt-adjusted operative anteversion than for operative inclination. Tilt-adjusted operative anteversion is significantly different between stable and unstable hips, and surgeons should therefore prioritize assessment of preoperative pelvic tilt and accurate placement in operative anteversion. With improvements in patient-specific cup orientation goals and acetabular component placement, further refinement of a safe zone with CT data may reduce the incidence of cup malposition and its associated complications. LEVEL OF EVIDENCE: Level III, diagnostic study.

Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy.

PURPOSE: Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-µs and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. MATERIAL AND METHODS: In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 µs, pulse energy 120-200 µJ, retinal spot size 200 µm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. RESULTS: Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. CONCLUSION: SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases.

Microcystic macular edema: retrograde maculopathy caused by optic neuropathy.

PURPOSE: To investigate retrograde axonal degeneration for its potential to cause microcystic macular edema (MME), a maculopathy that has been previously described in patients with demyelinating disease. To identify risk factors for MME and to expand the anatomic knowledge on MME. DESIGN: Retrospective case series. PARTICIPANTS: We included 117 consecutive patients and 180 eyes with confirmed optic neuropathy of variable etiology. Patients with glaucoma were excluded. METHODS: We determined age, sex, visual acuity, etiology of optic neuropathy, and the temporal and spatial characteristics of MME. Eyes with MME were compared with eyes with optic neuropathy alone and to healthy fellow eyes. With retinal layer segmentation we quantitatively measured the intraretinal anatomy. MAIN OUTCOME MEASURES: Demographic data, distribution of MME in the retina, and thickness of retinal layers were analyzed. RESULTS: We found MME in 16 eyes (8.8%) from 9 patients, none of whom had multiple sclerosis or neuromyelitis optica. The MME was restricted to the inner nuclear layer (INL) and had a characteristic perifoveal circular distribution. Compared with healthy controls, MME was associated with significant thinning of the ganglion cell layer and nerve fiber layer, as well as a thickening of the INL and the deeper retinal layers. Youth is a significant risk factor for MME. CONCLUSIONS: Microcystic macular edema is not specific for demyelinating disease. It is a sign of optic neuropathy irrespective of its etiology. The distinctive intraretinal anatomy suggests that MME is caused by retrograde degeneration of the inner retinal layers, resulting in impaired fluid resorption in the macula.

Improving cup positioning using a mechanical navigation instrument.

BACKGROUND: Although surgical navigation reduces the rate of malpositioned acetabular cups in total hip arthroplasty (THA), its use has not been widely adopted. As a result of our perceived need for simple and efficient methods of navigation, we developed a mechanical navigation device for acetabular cup orientation. QUESTIONS/PURPOSES: We assessed accuracy of cup orientation (mean error of cup inclination and anteversion) of a novel mechanical navigation device, percentage of outliers, length of operation, and compared the results with a series of CT-based computer-assisted THAs. METHODS: Cup orientation of 70 THAs performed using the mechanical navigation device was compared with a historical control group of 146 THAs performed using CT-based computer navigation. Postoperative cup orientation was measured using a validated two-dimensional/three-dimensional matching method. An outlier was defined outside a range of ± 10° from the planned inclination and/or anteversion. RESULTS: Using the mechanical navigation device, we observed a decrease in the errors of inclination (1.3° ± 3.4° [range, -6.6° to 8.2°] versus 3.5° ± 4.2° [-12.7° to 6.9°]), errors of anteversion (1.0° ± 4.1° [-8.8° to 9.5°] versus 3.0° ± 5.8° [-11.8° to 19.6°]), percentages of outliers (0% versus 9.6%), and length of operation (112 ± 22 [78-184] minutes versus 132 ± 18 [90-197] minutes) compared with CT-based navigation. CONCLUSIONS: Compared with CT-based surgical navigation, navigation of acetabular cup orientation using a mechanical device can be performed in less time, lower mean errors, and minimal equipment.

Feasibility of support vector machine learning in age-related macular degeneration using small sample yielding sparse optical coherence tomography data.

PURPOSE: A retrospective pilot study is conducted to demonstrate the utility of a novel support vector machine learning (SVML) algorithm in a small three-dimensional (3D) sample yielding sparse optical coherence tomography (spOCT) data for the automatic monitoring of neovascular (wet) age-related macular degeneration (wAMD). METHODS: From the anti-vascular endothelial growth factor injection database, 588 consecutive pairs of OCT volumes (57.624 B-scans) were selected in 70 randomly chosen wAMD patients treated with ranibizumab. The SVML algorithm was applied to 183 OCT volume pairs (17.934 B-scans) in 30 patients. Four independent, diagnosis-blinded retina specialists indicated whether wAMD activity was present between 100 pairs of consecutive OCT volumes (9800 B-scans) in the remaining 40 patients for comparison with the SVML algorithm and a non-complex baseline algorithm using only retinal thickness. The SVML algorithm was assessed using inter-observer variability and receiver operating characteristic (ROC) analyses. RESULTS: The retina specialists showed an average Cohen's κ of 0.57 ± 0.13 (minimum: 0.41, maximum: 0.83). The average κ between the proposed algorithm and the retina specialists was 0.62 ± 0.05 and 0.43 ± 0.14 between the baseline algorithm and the retina specialists. Using each of the four retina specialists as the reference, the proposed method showed a superior area under the ROC curve of 0.91 ± 0.03 compared to the ROC 0.81 ± 0.05 shown by the baseline algorithm. CONCLUSION: The SVML algorithm was as effective as the retina specialists were in detecting activity in wAMD. Support vector machine learning (SVML) may be a useful monitoring tool in wAMD suited for small samples that yield sparse OCT data possibly derived from self-measuring OCT-robots.

MARVIN: a medical research application framework based on open source software.

This paper describes the open source framework MARVIN for rapid application development in the field of biomedical and clinical research. MARVIN applications consist of modules that can be plugged together in order to provide the functionality required for a specific experimental scenario. Application modules work on a common patient database that is used to store and organize medical data as well as derived data. MARVIN provides a flexible input/output system with support for many file formats including DICOM, various 2D image formats and surface mesh data. Furthermore, it implements an advanced visualization system and interfaces to a wide range of 3D tracking hardware. Since it uses only highly portable libraries, MARVIN applications run on Unix/Linux, Mac OS X and Microsoft Windows.

Ligament balancing in TKA: evaluation of a force-sensing device and the influence of patellar eversion and ligament release.

Ligament balancing in total knee arthroplasty may have an important influence on joint stability and prosthesis lifetime. In order to provide quantitative information and assistance during ligament balancing, a device that intraoperatively measures knee joint forces and moments was developed. Its performance and surgical advantages were evaluated on six cadaver specimens mounted on a knee joint loading apparatus allowing unconstrained knee motion as well as compression and varus-valgus loading. Four different experiments were performed on each specimen. (1) Knee joints were axially loaded. Comparison between applied and measured compressive forces demonstrated the accuracy and reliability of in situ measurements (1.8N). (2) Assessment of knee stability based on condyle contact forces or varus-valgus moments were compared to the current surgical method (difference of varus-valgus loads causing condyle lift-off). The force-based approach was equivalent to the surgical method while the moment-based, which is considered optimal, showed a tendency of lateral imbalance. (3) To estimate the importance of keeping the patella in its anatomical position during imbalance assessment, the effect of patellar eversion on the mediolateral distribution of tibiofemoral contact forces was measured. One fourth of the contact force induced by the patellar load was shifted to the lateral compartment. (4) The effect of minor and major medial collateral ligament releases was biomechanically quantified. On average, the medial contact force was reduced by 20% and 46%, respectively. Large variation among specimens reflected the difficulty of ligament release and the need for intraoperative force monitoring. This series of experiments thus demonstrated the device's potential to improve ligament balancing and survivorship of total knee arthroplasty.

Development of a computer-assisted high-pressure Injection device for vertebroplasty.

A novel computer-assisted injection device for the delivery of highly viscous bone cements in vertebroplasty is presented. It addresses the shortcomings of manual injection systems ranging from low-pressure and poor level of control to device failure. The presented instrument is capable of generating a maximum pressure of 5000 kPa in traditional 6-ml syringes and provides an advanced control interface for precise cement delivery from outside radiation fields emitted by intraoperative imaging systems. The integrated real-time monitoring of injection parameters, such as flow-rate, volume, pressure, and viscosity, simplifies consistent documentation of interventions and establishes a basis for the identification of safe injection protocols on the longer term. Control algorithms prevent device failure due to overloading and provide means to immediately stop cement flow to avoid leakage into adjacent tissues.

Improved targeting device and computer navigation for accurate placement of brachytherapy needles.

Successful treatment of skull base tumors with interstitial brachytherapy requires high targeting accuracy for the brachytherapy needles to avoid harming vital anatomical structures. To enable safe placement of the needles in this area, we developed an image-based planning and navigation system for brachytherapy, which includes a custom-made mechanical positioning arm that allows rough and fine adjustment of the needle position. The fine-adjustment mechanism consists of an XYZ microstage at the base of the arm and a needle holder with two fine-adjustable inclinations. The rotation axes of the inclinations cross at the tip of the needle so that the inclinational adjustments do not interfere with the translational adjustments. A vacuum cushion and a noninvasive fixation frame are used for the head immobilization. To avoid mechanical bending of the needles due to the weight of attached tracking markers, which would be detrimental for targeting accuracy, only a single LED marker on the tail of the needle is used. An experimental phantom-based targeting study with this setup demonstrated that a positioning accuracy of 1.4 mm (rms) can be achieved. The study showed that the proposed setup allows brachytherapy needles to be easily aligned and inserted with high targeting accuracy according to a preliminary plan. The achievable accuracy is higher than if the needles are inserted manually. The proposed system can be linked to a standard afterloader and standard dosimetry planning module. The associated additional effort is reasonable for the clinical practice and therefore the proposed procedure provides a promising tool for the safe treatment of tumors in the skull base area.

A comparison study assessing the feasibility of ultrasound-initialized deformable bone models.

This article presents a feasibility and evaluation study for using 2D ultrasound in conjunction with our statistical deformable bone model within the scope of computer-assisted surgery. The final aim is to provide the surgeon with enhanced 3D visualization for surgical navigation in orthopedic surgery without the need for preoperative CT or MRI scans. We unified our earlier work to combine several automatic methods for statistical bone shape prediction and ultrasound segmentation and calibration to provide the intended rapid and accurate visualization. We compared the use of a tracked digitizing pointer and ultrasound for acquiring landmarks and bone surface points for the estimation of two cast proximal femurs.

Landmark detection for fusion of fundus and MRI toward a patient-specific multimodal eye model.

Ophthalmologists typically acquire different image modalities to diagnose eye pathologies. They comprise, e.g., Fundus photography, optical coherence tomography, computed tomography, and magnetic resonance imaging (MRI). Yet, these images are often complementary and do express the same pathologies in a different way. Some pathologies are only visible in a particular modality. Thus, it is beneficial for the ophthalmologist to have these modalities fused into a single patient-specific model. The goal of this paper is a fusion of Fundus photography with segmented MRI volumes. This adds information to MRI that was not visible before like vessels and the macula. This paper contributions include automatic detection of the optic disc, the fovea, the optic axis, and an automatic segmentation of the vitreous humor of the eye.

Time-Resolved Ultra-High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina Therapy.

PURPOSE: Selective retina therapy (SRT) is a novel treatment for retinal pathologies, solely targeting the RPE. During SRT, the detection of an immediate tissue reaction is challenging, as tissue effects remain limited to intracellular RPE photodisruption. Time-resolved ultra-high axial resolution optical coherence tomography (OCT) is thus evaluated for the monitoring of dynamic optical changes at and around the RPE during SRT. METHODS: An experimental OCT system with an ultra-high axial resolution of 1.78 µm was combined with an SRT system and time-resolved OCT M-scans of the target area were recorded from four patients undergoing SRT. Optical coherence tomography scans were analyzed and OCT morphology was correlated with findings in fluorescein angiography, fundus photography, and cross-sectional OCT. RESULTS: In cases in which the irradiation caused RPE damage proven by fluorescein angiography, the lesions were well discernible in time-resolved OCT images but remained invisible in fundus photography and cross-sectional OCT acquired after treatment. If RPE damage was introduced, all applied SRT pulses led to detectable signal changes in the time-resolved OCT images. The extent of optical signal variation seen in the OCT data appeared to scale with the applied SRT pulse energy. CONCLUSIONS: The first clinical results proved that successful SRT irradiation induces detectable changes in the OCT M-scan signal while it remains invisible in conventional ophthalmoscopic imaging. Thus, real-time high-resolution OCT is a promising modality to monitor and analyze tissue effects introduced by selective retina therapy and may be used to guide SRT in an automatic feedback mode (www.swissmedic.ch number, 2011-MD-0006).

Automatic Segmentation of the Eye in 3D Magnetic Resonance Imaging: A Novel Statistical Shape Model for Treatment Planning of Retinoblastoma.

PURPOSE: Proper delineation of ocular anatomy in 3-dimensional (3D) imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic resonance imaging (MRI) is presently used in clinical practice for diagnosis confirmation and treatment planning for treatment of retinoblastoma in infants, where it serves as a source of information, complementary to the fundus or ultrasonographic imaging. Here we present a framework to fully automatically segment the eye anatomy for MRI based on 3D active shape models (ASM), and we validate the results and present a proof of concept to automatically segment pathological eyes. METHODS AND MATERIALS: Manual and automatic segmentation were performed in 24 images of healthy children's eyes (3.29 ± 2.15 years of age). Imaging was performed using a 3-T MRI scanner. The ASM consists of the lens, the vitreous humor, the sclera, and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens, and the optic nerve, and then aligning the model and fitting it to the patient. We validated our segmentation method by using a leave-one-out cross-validation. The segmentation results were evaluated by measuring the overlap, using the Dice similarity coefficient (DSC) and the mean distance error. RESULTS: We obtained a DSC of 94.90 ± 2.12% for the sclera and the cornea, 94.72 ± 1.89% for the vitreous humor, and 85.16 ± 4.91% for the lens. The mean distance error was 0.26 ± 0.09 mm. The entire process took 14 seconds on average per eye. CONCLUSION: We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor, and the lens, using MRI. We additionally present a proof of concept for fully automatically segmenting eye pathology. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor.

A-mode ultrasound-based registration in computer-aided surgery of the skull.

OBJECTIVE: To evaluate the integration and accuracy of A (amplitude)-mode ultrasound-based surface matching for noninvasive registration of the head into a frameless computer-aided surgery system for otorhinology and skull base surgery. DESIGN: Experimental study and case series. SETTING: Academic medical center. PATIENTS: Twelve patients underwent anterior and paranasal skull base surgery with the routine use of a computer-aided surgery system. INTERVENTIONS: A computer-aided surgery system, based on an optoelectronic localizer, was used to track the skull and the surgical tools, including the A-mode ultrasound probe. The A-mode probe was a 10-MHz immersion transducer. An acoustic lens attached to the transducer focused the ultrasonic beam to a depth of 1 to 10 mm. Accuracy tests were performed for the ultrasound setup. Different surface point distributions were evaluated with respect to matching accuracy on a human cadaver skull specimen equipped with fiducial markers. The matching comparison was based on the fiducial registration error. For the clinical evaluation, the laboratory setup was transferred to the operating room. MAIN OUTCOME MEASURES: Noninvasive registration of the skull by using A-mode ultrasound in computer-aided surgery (practical and clinical measurements). RESULTS: The accuracy tests on the human skull specimen revealed that the mean +/- SD fiducial registration error was 1.00 +/- 0.19 mm in the best series for A-mode ultrasound surface matchings and was robust with respect to different sets of surface points. The mean +/- SD root mean square error from the 12 A-mode ultrasound matchings in the patient study was 0.49 +/- 0.20 mm. CONCLUSION: A-mode ultrasound surface matching can be used as a noninvasive and accurate registration procedure in computer-aided surgery of the head.

On the development and comparative evaluation of an ultrasound B-mode probe calibration method.

OBJECTIVE: Precise transducer calibration is an essential prerequisite for reliable surface registration based on ultrasound B-mode imaging devices. The clinical usage of a novel B-mode transducer calibration technique was evaluated and its attainable calibration precision assessed. MATERIALS AND METHODS: The Three Wire Method and the Cambridge Calibration Method were used as reference techniques to compare the efficiency, calibration precision and spatial requirements of the different techniques. A total of 20 calibration trials were performed using each technique and were statistically evaluated for accuracy and speed. RESULTS: The mean error characterizing the calibration precision of the Three Wire Method was 3.2 mm, obtained in a phantom with a volume of 14 x 10(6) mm(3) in 18.48 min. The Cambridge method resulted in a mean calibration error of 2.2 mm, but required a larger phantom with a volume of 35 x 10(6) mm3 to be used for a duration of 9.30 min. The proposed method yielded an average calibration error of 1.9 mm and was performed, on average, in 2 min using a phantom with a size smaller than 1 x 10(6) mm3. CONCLUSIONS: The suggested calibration method offers decreased time and space while retaining an equivalent calibration precision when compared to established reference methods.

Noninvasive referencing of intraocular tumors for external beam radiation therapy using optical coherence tomography: a proof of concept.

PURPOSE: External beam radiation therapy is currently considered the most common treatment modality for intraocular tumors. Localization of the tumor and efficient compensation of tumor misalignment with respect to the radiation beam are crucial. According to the state of the art procedure, localization of the target volume is indirectly performed by the invasive surgical implantation of radiopaque clips or is limited to positioning the head using stereoscopic radiographies. This work represents a proof-of-concept for direct and noninvasive tumor referencing based on anterior eye topography acquired using optical coherence tomography (OCT). METHODS: A prototype of a head-mounted device has been developed for automatic monitoring of tumor position and orientation in the isocentric reference frame for LINAC based treatment of intraocular tumors. Noninvasive tumor referencing is performed with six degrees of freedom based on anterior eye topography acquired using OCT and registration of a statistical eye model. The proposed prototype was tested based on enucleated pig eyes and registration accuracy was measured by comparison of the resulting transformation with tilt and torsion angles manually induced using a custom-made test bench. RESULTS: Validation based on 12 enucleated pig eyes revealed an overall average registration error of 0.26 ± 0.08° in 87 ± 0.7 ms for tilting and 0.52 ± 0.03° in 94 ± 1.4 ms for torsion. Furthermore, dependency of sampling density on mean registration error was quantitatively assessed. CONCLUSIONS: The tumor referencing method presented in combination with the statistical eye model introduced in the past has the potential to enable noninvasive treatment and may improve quality, efficacy, and flexibility of external beam radiotherapy of intraocular tumors.

Retinal layer measurements after successful macula-off retinal detachment repair using optical coherence tomography.

PURPOSE: Optical coherence tomography (OCT) was used to analyze the thickness of various retinal layers of patients following successful macula-off retinal detachment (RD) repair. METHODS: Optical coherence tomography scans of patients after successful macula-off RD repair were reanalyzed with a subsegmentation algorithm to measure various retinal layers. Regression analysis was performed to correlate time after surgery with changes in layer thickness. In addition, patients were divided in two groups. Group 1 had a follow-up period after surgery of up to 7 weeks (range, 21-49 days). In group 2, the follow-up period was >8 weeks (range, 60-438 days). Findings were compared to a group of age-matched healthy controls. RESULTS: Correlation analysis showed a significant positive correlation between inner nuclear-outer plexiform layer (INL-OPL) thickness and time after surgery (P=0.0212; r2=0.1551). Similar results were found for the ellipsoid zone-retinal pigment epithelium complex (EZ-RPE) thickness (P=0.005; r2=0.2215). Ganglion cell-inner plexiform layer thickness (GCL-IPL) was negatively correlated with time after surgery (P=0.0064; r2=0.2101). For group comparison, the retinal nerve fiber layer in both groups was thicker compared to controls. The GCL-IPL showed significant thinning in group 2. The outer nuclear layer was significantly thinner in groups 1 and 2 compared to controls. The EZ-RPE complex was significantly thinner in groups 1 and 2 compared to controls. In addition, values in group 1 were significantly thinner than in group 2. CONCLUSIONS: Optical coherence tomography retinal layer thickness measurements after successful macular-off RD repair revealed time-dependent thickness changes. Inner nuclear-outer plexiform layer thickness and EZ-RPE thickness was positively correlated with time after surgery. Ganglion cell-inner plexiform layer thickness was negatively correlated with time after surgery.

Quantitative analysis of fluorescence lifetime measurements of the macula using the fluorescence lifetime imaging ophthalmoscope in healthy subjects.

PURPOSE: Fundus autofluorescence (FAF) cannot only be characterized by the intensity or the emission spectrum, but also by its lifetime. As the lifetime of a fluorescent molecule is sensitive to its local microenvironment, this technique may provide more information than fundus autofluorescence imaging. We report here the characteristics and repeatability of FAF lifetime measurements of the human macula using a new fluorescence lifetime imaging ophthalmoscope (FLIO). METHODS: A total of 31 healthy phakic subjects were included in this study with an age range from 22 to 61 years. For image acquisition, a fluorescence lifetime ophthalmoscope based on a Heidelberg Engineering Spectralis system was used. Fluorescence lifetime maps of the retina were recorded in a short- (498-560 nm) and a long- (560-720 nm) spectral channel. For quantification of fluorescence lifetimes a standard ETDRS grid was used. RESULTS: Mean fluorescence lifetimes were shortest in the fovea, with 208 picoseconds for the short-spectral channel and 239 picoseconds for the long-spectral channel, respectively. Fluorescence lifetimes increased from the central area to the outer ring of the ETDRS grid. The test-retest reliability of FLIO was very high for all ETDRS areas (Spearman's ρ = 0.80 for the short- and 0.97 for the long-spectral channel, P < 0.0001). Fluorescence lifetimes increased with age. CONCLUSIONS: The FLIO allows reproducible measurements of fluorescence lifetimes of the macula in healthy subjects. By using a custom-built software, we were able to quantify fluorescence lifetimes within the ETDRS grid. Establishing a clinically accessible standard against which to measure FAF lifetimes within the retina is a prerequisite for future studies in retinal disease.

Graph-based multi-surface segmentation of OCT data using trained hard and soft constraints.

Optical coherence tomography (OCT) is a well-established image modality in ophthalmology and used daily in the clinic. Automatic evaluation of such datasets requires an accurate segmentation of the retinal cell layers. However, due to the naturally low signal to noise ratio and the resulting bad image quality, this task remains challenging. We propose an automatic graph-based multi-surface segmentation algorithm that internally uses soft constraints to add prior information from a learned model. This improves the accuracy of the segmentation and increase the robustness to noise. Furthermore, we show that the graph size can be greatly reduced by applying a smart segmentation scheme. This allows the segmentation to be computed in seconds instead of minutes, without deteriorating the segmentation accuracy, making it ideal for a clinical setup. An extensive evaluation on 20 OCT datasets of healthy eyes was performed and showed a mean unsigned segmentation error of 3.05 ±0.54 µm over all datasets when compared to the average observer, which is lower than the inter-observer variability. Similar performance was measured for the task of drusen segmentation, demonstrating the usefulness of using soft constraints as a tool to deal with pathologies.