bluuebunny/crossref_metadata_2025 huggingface dataset:
Medial glenohumeral ligament reconstruction for ex-vivo medial glenohumeral luxation in the dog
Authors: Kerwin S. C. , Hosgood G. , Williams J. , Ringwood P. B.
Published: March 2018

The range of motion (ROM) and instant centre of motion (ICM) of the isolated glenohumeral joint were determined after experimentally induced medial glenohumeral luxation was repaired with a prosthetic medial glenohumeral ligament (MGHL) and biceps brachii tendon transposition (BTT) in 10 canine cadaver forelimbs. In this ex-vivo model, the BTT altered the ROM and ICM significantly more than MGHL reconstruction.
Surgical reconstruction of ectrodactyly deformity in four dogs
Authors: McKee W. M. , Mitchell R. A. S. , Innes J. F. , Lascelles B. D. X. , Johnson K. A.
Published: March 2018

Four immature dogs were presented with ectrodactyly. Two dogs were initially treated with distraction osteogenesis of a hypoplastic ulna and all had surgical correction of the cleft deformity. In each case proximal metacarpal apposition with or without carpal arthrodesis formed the basis of surgical treatment. Follow-up information was available for three cases and all showed improved limb function. Corrective surgery appears to be a viable alternative to amputation for treatment of ectrodacty1y.
Clinical evaluation of prosthetic medial glenohumeral ligament repair in the dog (ten cases)
Authors: Breshears L. , Staatz A. , Kudnig S. , Fitch R. B.
Published: March 2018

This is a clinical evaluation of ten clinical cases of medial shoulder luxation and instability repaired using prosthetic medial glenohumeral ligament sutures intended to replicate the mechanical function of the medial glenohumeral ligament, thereby restoring normal motion to the scapulohumeral joint without altering regional anatomy. Eight dogs presented with medial shoulder instability, one case with congenital shoulder luxation and one traumatic induced complete shoulder luxation. Evaluations were performed by gait, orthopedic and radiographic examinations as well as owner questionnaire. Nine of ten dogs had good to excellent clinical outcomes. This paper presents a surgical technique that restores normal stability, congruency, mobility and function to the shoulder joint without altering regional anatomy.

This case series of ten clinical cases describes a surgical technique for stabilization of medial shoulder luxation and instability intended to replicate the function of the medial glenohumeral ligament, thereby restoring normal motion to the scapulohumeral joint without altering regional anatomy.
A comparison of the effects of joint immobilisation, twice-daily passive motion, and voluntary motion on articular cartilage healing in sheep
Authors: Frame K. , Burbidge H. M. , Thompson K. , Firth E. C. , Bruce W. J.
Published: March 2018

In this study, articulated transarticular external skeletal fixators were used to examine the effects of joint immobilisation, twice-daily passive range-of-motion exercises, and voluntary motion on articular cartilage healing and other joint parameters. Abaxial articular cartilage lesions demonstrated superior cartilage healing to axial lesions. Twice-daily passive range of motion exercises failed to improve the quality of articular cartilage repair when compared with joint immobilisation. Voluntary motion resulted in superior articular cartilage repair tissue with maintenance of near normal cartilage architecture, proteoglycan staining, synovial fluid cell counts and specific gravity, and joint range-of-motion.
Investigation of a modified reverse saphenous conduit flap in the dog
Authors: Fowler D. , Shmon C. , Harder M. , Bebchuk T. , Isakow K.
Published: March 2018

This experimental study investigated the feasibility of a modified reverse saphenous conduit flap (RSCF). Modified reverse saphenous conduit flaps were harvested bilaterally in 11 experimental dogs. Each flap was based on preservation of either the cranial or caudal branch of the medial saphenous artery and vein, but not both. In five dogs, flaps were elevated from a medial femoral donor site and subsequently sutured into their normal anatomical positions (orthotopic flap). Four of five orthotopic flaps based on the cranial saphenous vessels and three of five orthotopic flaps based on the caudal saphenous vessels survived in their entirety. Orthotopic flaps demonstrated an “all or none” survival pattern. In the second phase, flaps were elevated bilaterally from a medial femoral donor site and transferred to a metatarsal skin defect using a bridging incision in six dogs (heterotopic flaps). Two of six heterotopic flaps, based on the cranial saphenous vessels and two of six based on the caudal saphenous vessels, survived in their entirety. Three flaps, based on the cranial pedicle and two flaps based on a caudal pedicle, experienced partial survival. One flap based on the cranial pedicle and two flaps based on the caudal pedicle experienced total flop failure. Survival of the modified reverse saphenous conduit flap, as described herein, is inconsistent and, therefore, its use cannot be recommended. Additionally, the results suggest that the reverse saphenous conduit flap should be used with caution in cases where trauma or surgery has embarrassed the integrity of either the cranial or caudal vascular branch.
Treatment of carpometacarpal and middle carpal joint hyperextension injuries with partial carpal arthrodesis using a cross pin technique: 21 cases
Authors: Lenehan T. M. , Davidson C. D. , Tarvin G. B. , Carlson K. R. , Hayes A. , Haburjak J. J.
Published: March 2018

The cross-pin technique presented here was technically easy to perform, allowed latitude in pin placement, had manageable post-operative issues and allowed for facilitated pin removal. Objective patient inclusion criteria remain to be established.
Canine keratinocyte culture and use of a cultured epidermal autograft in a dog
Authors: Stanley M. A. , White R. A. S. , Anderson D. M.
Published: March 2018

A seven month old female Yorkshire Terrier was admitted with severe contracture and scarring of the ventral abdomen, thorax and limbs, after a scald injury. Surgical management consisted of multiple releasing and reconstruction skin flaps. Keratinocytes, harvested from a 1 cm2 full thickness skin biopsy, were cultured on a lawn of irradiated feeder cells, and used as a cultured epithelial autograft on the remaining skin deficits. Epithelialisation of the deficits was complete at the first dressing change, five days after application. This is the first report of successful culture of canine keratinocytes suitable for use in skin reconstruction in a clinical case.
Proximal tibial osteotomy for the repair of cranial cruciate-deficient stifle joints in dogs
Authors: Tepic S. , Montavon P. M. , Damur D. M.
Published: March 2018

A proximal tibial osteotomy technique for the repair of complete or partial rupture of the cranial cruciate ligament in dogs is described and the results of a series of 100 consecutively operated stifle joints are presented. Although the majority of dogs regained full function of the operated limb within four months of surgery, the overall complication rate was high.
Radiographic findings related to interlocking nailing: windshield-wiper effect, and locking screw failure
Authors: Diaz-Bertrana M. C. , Puchol J. L. , Franch J. , Durall I.
Published: March 2018

The purpose of this paper is to describe two uncommon radiographic findings related to the use of interlocking nails (ILNs) fixation. The first one is a radiolucency located around the distal tip of the nail observed in three clinical cases. This radiographic sign was similar to one described in human medicine known as “windshield-wiper effect” and observed around the tip of the screw used for slipped capital femoral epiphysis in children, and also in association with intramedullary nail treatment. In one of our clinical cases, the radiolucency observed four weeks post-surgery completely disappeared two months later, unfortunately a follow-up radiograph was not available in the two other cases. The second complication is related to three screw-bendings observed in the centre of the nail in two clinical cases. In one case both proximal screws appeared to be radiographically bent, and non-union of the fracture was observed five months after surgery. The screws were in fact broken, instead of being bent, which we were able to determine in the second surgery. In the other clinical case, the screw appeared to be radiographically bent, but the fracture had healed. We could not confirm whether the screw was bent or broken because the owner refused to permit removal of the implant. When bone healing complications are detected, bent screws should be checked and suspected of being broken.
Effect of stem flattening on rotational stability of a canine femoral total hip component in polymethylmethacrylate cement
Authors: Schulz K. S. , Kass P. H. , Stover S. M. , Mason D. R.
Published: March 2018

This study was designed to determine the effect of flattening the lateral aspect of a commercially available femoral prosthesis on its rotational stability in polymethylmethacrylate cement. Five standard design and five laterally flattened size 7 canine femoral components were evaluated. The stems were embedded in commercially available medical grade polymethylmethacrylate and rotated 15° while torque and angular displacement data were collected. The stiffness, yield and failure variables were compared between commercial and flattened stems. None of the mechanical testing variables were statistically different between commercial and flattened stems although all of the mean values for flattened stems were higher (1-30%) than mean values for commercial stems. Rotational stability of a canine total hip replacement femoral component was not significantly enhanced by the flattened component design modification evaluated by the testing protocol in this study.
The use of stacked T-plating in dogs
Authors: von Pfeil D. J. F. , Roush J. K.
Published: March 2018

Dogs with fractures of the distal femur (one case), ilium (two cases) and a corrective osteotomy of the distal tibia (one case) underwent internal fixation using two 3.5-mm T-plates, applied in stacked fashion. Due to the specific configuration of the fractures as well as the size of the dogs, stacked T-plating was considered the most reliable technique to achieve satisfactory repair. All of the cases had “excellent” to “good” outcomes. The clinical experience with these four cases supports the utility of stacked T-plating in fractures with one very short end fragment. Stacked T-plating seems to have distinct advantages over a single 3.5-mm dynamic compression plate. However, due to the small number of cases presented in this report, there is a need for further clinical evaluation and biomechanical studies.
A Finite Element Model of the Proximal Sesamoid Bones of the Horse Under Different Loading Conditions
Authors: Cheung T. K. , Thompson K. N.
Published: March 2018

Fracture of the proximal sesamoid bones is a common injury of racing horses, usually resulting from over-dorsiflexion of the metacarpophalangeal joint. The purpose of this study was to develop a computer-aided method utilizing stereo-radiography, computed tomography, and finite element method to determine three-dimensional stress distribution in the proximal sesamoid bones during metacarpophalangeal joint dorsiflexion. The stress pattern was characterized by a compressive component on the articular part of the bone and a tensile component on the non-articular part of the bone. Maximum principal stresses were 2.5, 9.1 and 15.5 MPa and minimum principal stresses were -1.9, -9. 2 and -14. 9 MPa for metacarpophalangeal joint angles of 140°, 125° and 110°, respectively. The distal portion of the articular part of the bone experienced the largest compressive stress. In this study changes in the orientation and magnitude of the ligament force vectors did not significantly change stress patterns of the proximal sesamoid bone.

This study was designed to determine stress patterns of the proximal sesamoid bones in horses. Stress patterns were determined by finite element method analysis. Compressive stresses were present on the articular side, and tensile stresses were present on the nonarticular side of the bones. The magnitude of load applied to the bone did not appreciably change the pattern of stresses.
Pancarpal Arthrodesis in a Cat: A Case Report and Anatomical Study
Authors: Goldsmid Sarah , Simpson D.
Published: March 2018

A carpometacarpal hyperextension injury in a cat was treated by pancarpal arthrodesis, following the failure of conservative treatment. An 8-hole 1.5 mm mini plate was placed on the dorsal aspect of the distal radius, carpus and third metacarpal bone. An aluminium spoon splint was used for six weeks postoperatively, until radio-graphs revealed bone union. The body weights and the dimensions of the distal radius, radiocarpal bone and third metacarpal bone from the left limb of 15 cadavers were recorded in order to aid the selection of appropriate implants for future cases.

Pancarpal arthrodesis was used to treat a cat with a carpometacarpal hyperextension injury. The use of an 8-hole 1.5 mm mini plate applied to the dorsal surface of the carpus, in combination with limb splinting provided effective stabilization. An excellent functional result was obtained. Measurements of the radius, radial carpal and third metacarpal bones from 15 cadavers suggest that 1.5 mm bone screws are the largest that should be used for carpal arthrodesis in the average sized cat.
Prospective Clinical Study of Biodegradable Poly-L-Lactide Implant as an Augmentation Device with Fascia Lata in Cranial Cruciate Ligament Repair in the Dog: Early Results
Authors: Laitinen O.
Published: March 2018

Twenty-seven dogs with cranial cruciate ligament (CCL) rupture were treated with intra-articular reconstruction using a biodegradable poly-Llactide (PLLA) implant as an augmentation device, with a fascia lata graft in 12 dogs or with a fascia lata graft alone in 15 dogs. The clinical assessment was performed two, 12, and 24 weeks postoperatively. At 12 weeks the stability of the stifle joints was significantly better (p < 0.05) in the fascia lata-PLLA (FL-PLLA) group, compared to the fascia lata (FL) group, because the PLLA augmentation device gave additional support to the fascia lata graft in the early healing phase. At 24 weeks 11 dogs (92%) of the FL-PLLA group and 13 dogs (87%) of the FL group were free of lameness. Radiographically, degenerative changes defined as osteophyte formation were found preoperatively in 10 dogs in the FLPLLA group and 11 dogs in the FL group. The postoperative degenerative changes increased in four dogs in the FL-PLLA group and five dogs in the FL group at 12 weeks. At 24 weeks in two dogs in both groups the degenerative changes had advanced.

A biodegradable poly-L-lactide (PLLA) augmentation device was used to reinforce a fascia lata graft in cranial cruciate ligament repair in 12 dogs and compared clinically and radio-graphically with a fascia lata replacement technique in 15 dogs. Clinically, at 12 weeks the stability of the stifle joints was significantly better (p <0.05) using the PLLA im-plant with the fascia lata. At 24 weeks significant differences were not found in the clinical nor radiographic outcome between the two groups.
Historical Editorial – Nonunion
Authors: Sumner-Smith G.
Published: March 2018

“Why is my pain perpetual and my wound incurable, which refuseth to heal?” Jeremiah XV. 18.
Technique and Indications of a Prosthetic Capsule for Repair of Recurrent and Chronic Coxofemoral Luxations
Authors: Braden T. D. , Johnson M. E.
Published: March 2018

scribed for the treatment of recurrent coxofemoral luxations. It utilizes a large suture material which is woven between the femur and acetabulum and acts as a “prosthetic capsule”. This technique has been used in 22 cases of coxofemoral luxations at Michigan State University Veterinary Clinical Centre with a 66.6% success rate.
Traumatic Exogenous Uveitis
Authors: Wilcock B. P. , Williams Melanie M.
Published: March 2018

A young dog was presented to the veterinary ophthalmology service with marked unilateral anterior uveitis and blindness, extreme pain, anorexia and weight loss. Porcupine quill migration into the orbital and ocular tissues was suspected due to an encounter with a porcupine three weeks previously. Surgical orbital extenteration and exploration revealed two porcupine quill segments penetrating the oculus bulbi and extending into the orbital tissues. The location and movement of the quills within the globe and orbital muscle cone during mastication accounted for the deep pain, anorexia and weight loss. The quills incited a sterile foreign body reaction with fibroplasia and granulation tissue formation in the sclera and ciliary body. The eye was avisual due to the anterior segment structural and inflammatory changes.
An Animal Model for the Implantation of a Bone Liner in the Flexible Implant Arthroplasty
Authors: McGehee J. A. , Swanson A. B. , Braden T. D.
Published: March 2018

A retrospective study of silicone elastomer implants used clinically as a flexible implant in the metacarpophalangeal (MP) and proximal interphalangeal (PIP) joints in humans indicated a 7.6% implant fracture failure rate. Implant fractures appeared to occur from tear propagation due to damage resulting from the impingement of the sharp bone edges upon the implant’s surface. A protective synthetic bone liner was devised to reduce in vivo damage and prevent implant failures. The rabbit stifle was used as the animal model for the human metacarpophalangeal and proximal interphalangeal joint and 73 implant arthroplasties were successfully performed.
Suggestions for the Reduction of Fractures
Authors: Brinker W. O.
Published: March 2018

Various methods of accomplishing fracture reduction are presented.
Partial Carpal Arthrodesis in the Horse
Authors: Taylor J. R. , Welch R. D. , Stricklin J. B. , Auer J. A. , Watkins J. P.
Published: March 2018

Over a period of 6 years, four horses and two foals were treated with partial carpal arthrodesis. The problems treated included one luxation each of the carpometacarpal, and the antebrachiocarpal joint, as well as one subluxation of the carpometacarpal and the middle carpal joints. The luxations developed secondary to rupture of the joint capsule as well as one or two collateral ligaments. In three cases, comminuted fractures of the distal row of carpal bones, complicated in one of these cases by a fracture of the intermediate carpal bone, were treated. Arthrodesis by internal fixation using T-plates or dynamic compression plates of various sizes was successful in salvaging some of the animals. The various cases are discussed in detail as to technique and reason of its application. One horse was euthanatized, two are presently used for pleasure riding and three horses are used for breeding purposes. The horses treated by means of arthrodesis were compared to one case of luxation of the middle carpal joint, which was treated unsuccessfully by external coaptation alone.

The results of partial carpal arthrodesis in four horses and two foals are described, as are the techniques employed and the results.
Marker Identification and Classification of Cancer Types Using Gene Expression Data and SIMCA
Authors: Luchini A. , Di Bello C. , Bicciato S.
Published: March 2018

Objectives:
High-throughput technologies are radically boosting the understanding of living systems, thus creating enormous opportunities to elucidate the biological processes of cells in different physiological states. In particular, the application of DNA micro-arrays to monitor expression profiles from tumor cells is improving cancer analysis to levels that classical methods have been unable to reach. However, molecular diagnostics based on expression profiling requires addressing computational issues as the overwhelming number of variables and the complex, multi-class nature of tumor samples. Thus, the objective of the present research has been the development of a computational procedure for feature extraction and classification of gene expression data.

Methods:
The Soft Independent Modeling of Class Analogy (SIMCA) approach has been implemented in a data mining scheme, which allows the identification of those genes that are most likely to confer robust and accurate classification of samples from multiple tumor types.

Results:
The proposed method has been tested on two different microarray data sets, namely Golub’s analysis of acute human leukemia [1] and the small round blue cell tumors study presented by Khan et al. [2]. The identified features represent a rational and dimensionally reduced base for understanding the biology of diseases, defining targets of therapeutic intervention, and developing diagnostic tools for classification of pathological states.

Conclusions:
The analysis of the SIMCA model residuals allows the identification of specific phenotype markers. At the same time, the class analogy approach provides the assignment to multiple classes, such as different pathological conditions or tissue samples, for previously unseen instances.
Surface EMG Crosstalk Evaluated from Experimental Recordings and Simulated Signals
Authors: Merletti R. , Indino B. , Graven-Nielsen T. , Farina D.
Published: March 2018

Objectives:
Surface EMG crosstalk is the EMG signal detected over a non-active muscle and generated by a nearby muscle. The aim of this study was to analyze the sources of crosstalk signals in surface EMG recordings and to discuss methods proposed in the literature for crosstalk quantification and reduction.

Methods:
The study is based on both simulated and experimental signals. The simulated signals are generated by a structure based surface EMG signal model. Signals were recorded with both intramuscular and surface electrodes and single motor unit surface potentials were extracted with the spike triggered averaging approach. Moreover, surface EMG signals were recorded from electrically stimulated muscles.

Results:
From the simulation and experimental analysis it was clear that the main determinants of crosstalk are non-propagating signal components, generated by the extinction of the intracellular action potentials at the tendons. Thus, crosstalk signals have a different shape with respect to the signals detected over the active muscle and contain high frequency components.

Conclusions:
Since crosstalk has signal components different from those dominant in case of detection from near sources, commonly used methods to quantify and reduce crosstalk, such as the cross-correlation coefficient and high-pass temporal filtering, are not reliable. Selectivity of detection systems must be discussed separately as selectivity with respect to propagating and non-propagating signal components. The knowledge about the origin of crosstalk signal constitutes the basis for crosstalk interpretation, quantification, and reduction.
Effects of Subthreshold Shocks on Wavelet Propagation during Atrial Fibrillation in Humans
Authors: Bartolini P. , Calcagnini G. , Censi F. , Macioce R. , Michelucci A. , Poli S. , Barbaro V.
Published: March 2018

Objectives:
Our objectives are: first to investigate the effects of internal cardioversion energies on the wave fronts propagation in the right atrium immediately after the energy delivery; second, to track the time course of these effects.

Methods:
The study is based on a measure of organization of the endoatrial electrograms obtained by a multipolar basket catheter inserted in the right atrium. We estimated the level of organization by computing the percentage of points laying on the signal baseline (i.e., number of occurrences, NO). NO values were computed on two-second long windows. Six non-overlapped windows were selected, one just before and five just after the last unsuccessful shock.

Results:
Immediately after the shock most of the patients exhibited an increase in the organization patterns. This increase was more evident in those patients with rather disorganized patterns and higher energy threshold. This effect fades within a few seconds after the shock delivery.

Conclusions:
Our data confirm the idea that the electrical shock causes a widespread extinction of electrical wavefronts, which regenerates after the shock. Since an increase of organization may lead to a reduction of energy threshold, a potential application of these findings might consist in the delivery of multiple subthreshold shocks instead of a single one.
Time-Frequency Analysis of Brain Electrical Activity – Adaptive Approximations
Authors: Durka P. J. , ygierewicz J. Z , Blinowska K. J.
Published: March 2018

Objectives:
We present an approach to time-frequency analysis of bioelectrical signals.

Methods:
The method relays on the decomposition of the signal into a set of waveforms that have good localization both in time and in frequency. The waveforms belong to a highly redundant set of functions – allowing for a very accurate description of signal components.

Results:
Properties of the method are illustrated by simulations and applications to EEG.

Conclusion:
The presented method delivers a common formalism suitable for describing both gross statistical properties of structures present in bioelectrical signals, as well as microstructure of chosen phenomena.
Characterization of Heart Rate Variability Changes Following Asphyxia in Rats
Authors: Moraru L. , Cimponeriu L. , Tong S. , Thakor N. , Bezerianos A.
Published: March 2018

Objectives:
A non-invasive method to monitor the functioning of the autonomous nervous system consists in heart rate variability (HRV) analysis. The aim of this study was to investigate the changes on HRV after an asphyxia experiment in rats, using several linear (time and frequency domain) and nonlinear parameters (approximate entropy, SD1 and SD2 indices derived from Poincare plots).

Methods:
The experiments involved the study of HRV changes after cardiac arrest (CA) resulting from 5 min of hypoxia and asphyxia, followed by manual resuscitation and return of spontaneous circulation. 5 min stationary periods of RR intervals were selected for further analysis from 5 rats in following distinct situations: 1) baseline, 2) 30 min after CA, 3) 60 min after CA, 4) 90 min after CA, 5) 120 min after CA, 6) 150 min after CA. The ANS contribution has been delineated based on time and frequency domain analysis.

Results and Conclusions:
The results indicate that the recovery process following the asphyxia cardiac arrest reflects the impaired functioning of the autonomic nervous system. Both linear and nonlinear parameters track the different phases of the experiment, with an increased sensitivity displayed by the approximate entropy (ApEn). After 150 min the ApEn RRI parameter recovers to its baseline value. The results forward the ApEn as a more sensitive parameter of the recovery process following the asphyxia.
Advances in Biomedical Image Analysis
Authors: Meinzer H. P. , Tolxdorff T. , Lehmann T. M.
Published: March 2018

Starting from raw data files coding eight bits of gray values per image pixel and identified with no more than eight characters to refer to the patient, the study, and technical parameters of the imaging modality, biomedical imaging has undergone manifold and rapid developments. Today, rather complex protocols such as Digital Imaging and Communications in Medicine (DICOM) are used to handle medical images. Most restrictions to image formation, visualization, storage and transfer have basically been solved and image interpretation now sets the focus of research. Currently, a method-driven modeling approach dominates the field of biomedical image processing, as algorithms for registration, segmentation, classification and measurements are developed on a methodological level. However, a further metamorphosis of paradigms has already started. The future of medical image processing is seen in task-oriented solutions integrated into diagnosis, intervention planning, therapy and followup studies. This alteration of paradigms is also reflected in the literature. As German activities are strongly tied to the international research, this change of paradigm is demonstrated by selected papers from the German annual workshop on medical image processing collected in this special issue.
Automated Hybrid TACT® Volume Reconstructions
Authors: Linnenbrügger N. I. , Webber R. L. , Kobbelt L. P. , Lehmann T. M.
Published: March 2018

Objectives:
To design, implement in Java™, and evaluate a method and means for the automated localization of artificial landmarks in optical images for tuned-aperture computed tomography® (TACT®) that allows the replacement of radiographic with optical landmarks.

Methods:
Circular, colored, optical landmarks were designed to provide flexibility with regard to landmark constellation, imaging equipment, and lighting conditions. The landmark detection was based on Hough transforms (HT) for ellipses and lines. The HT for ellipses was extended to enable selective detection of bright ellipses on a dark background and vice versa, and the number of irrelevant votes in the accumulator arrays was reduced. An experiment was performed in vitro to test the automated landmark localization scheme, verify registration accuracy, and measure the required computation time.

Results:
A visual evaluation of the tomographic slices that were produced using the new method revealed good registration accuracy. A comparison to tomographic slices similarly produced by means of conventional TACT showed identical results. The algorithm ran sufficiently fast on standard hardware to allow landmark localization in “real time” during successive image acquisition in clinical applications.

Conclusions:
The proposed method provides robust automated localization of landmarks in optical images. Using a hybrid imaging system, TACT can now be clinically applied without manual interaction of a human operator and without radiopaque landmarks, which might cover anatomic details of diagnostic interest.
A Linear Programming Approach to Limited Angle 3D Reconstruction from DSA Projections
Authors: Schüle T. , Schnörr C. , Hornegger J. , Weber S.
Published: March 2018

Objectives:
We investigate the feasibility of binary-valued 3D tomographic reconstruction using only a small number of projections acquired over a limited range of angles.

Methods:
Regularization of this strongly ill-posed problem is achieved by (i) confining the reconstruction to binary vessel/non-vessel decisions, and (ii) by minimizing a global functional involving a smoothness prior.

Results:
Our approach successfully reconstructs volumetric vessel structures from three projections taken within 90°. The percentage of reconstructed voxels differing from ground truth is below 1%.

Conclusion:
We demonstrate that for particular applications – like Digital Subtraction Angiography – 3D reconstructions are possible where conventional methods must fail, due to a severely limited imaging geometry. This could play an important role for dose reduction and 3D reconstruction using non-conventional technical setups.
A Reliable and Efficient Method for Cerebral Ventricular Volumetry in Pediatric Neuroimaging
Authors: Millar W. S. , Klinghammer O. , Durkin M. S. , Tulipano P. K. , Peitgen H.-O. , Hahn H. K.
Published: March 2018

Objectives:
Cerebral ventricular volume has the potential to become an important parameter in quantitative neurological diagnosis. However, no accepted methodology for routine clinical use exists to date. We sought a robust, reproducible, and fast technique to evaluate cerebral ventricular volume in young children.

Methods:
We describe a novel volumetric methodology to segment and visualize intracerebral fluid spaces and to quantify ventricular volumes. The method is based on broadly available T1 weighted volumetric magnetic resonance (MR) imaging, an interactive watershed transform, and a fully automated histogram analysis. We evaluated this volumetric methodology with 34 clinical volumetric MR datasets from non-sedated children (age 6-7 y) with a history of prematurity and low birth weight (≤ 1500 g) obtained during a prospective study.

Results:
The methodology, with adaptation for small ventricular size, was capable of evaluating all 34 of the pediatric datasets for cerebral ventricular volume. The method was a) robust for normal and pathological anatomy, b) reproducible, c) fast with less than five minutes for image analysis, and d) equally applicable to children and adults.

Conclusions:
Clinical brain ventricular volume calculations in non-sedated children can be performed using routine MR imaging besides efficient three-dimensional segmentation and histogram analysis with results that are robust and reproducible.
Atlas-based Recognition of Anatomical Structures and Landmarks and the Automatic Computation of Orthopedic Parameters
Authors: Handels H. , Plötz W. , Pöppl S. J. , Ehrhardt J.
Published: March 2018

Objective:
This paper describes methods for the automatic atlas-based segmentation of bone structures of the hip, the automatic detection of anatomical point landmarks and the computation of orthopedic parameters to avoid the interactive, time-consuming preprocessing steps for the virtual planning of hip operations.

Methods:
Based on the CT data of the Visible Human Data Sets, two three-dimensional atlases of the human pelvis have been built. The atlases consist of labeled CT data sets, 3D surface models of the separated structures and associated anatomical point landmarks. The atlas information is transferred to the patient data by a non-linear gray value-based registration algorithm. A surface-based registration algorithm was developed to detect the anatomical landmarks on the patient’s bone structures. Furthermore, a software tool for the automatic computation of orthopedic parameters is presented. Finally, methods for an evaluation of the atlas-based segmentation and the atlas-based landmark detection are explained.

Results:
A first evaluation of the presented atlas-based segmentation method shows the correct labeling of 98.5% of the bony voxels. The presented landmark detection algorithm enables the precise and reliable localization of orthopedic landmarks. The accuracy of the landmark detection is below 2.5 mm.

Conclusion:
The atlas-based segmentation of bone structures, the atlas-based landmark detection and the automatic computation of orthopedic measures are suitable to essentially reduce the time-consuming user interaction during the pre-processing of the CT data for the virtual three-dimensional planning of hip operations.
An Approach to Knowledge Base Construction Based on Expert Opinions
Authors: Talmon J. L. , Renier W. O. , Hasman A. , Ast J. F.
Published: March 2018

Objectives:
To describe, validate and demonstrate an approach for knowledge base construction based on expert opinions.

Methods:
A knowledge base containing the frequency of occurrence of manifestations in epileptic seizures is constructed based on information provided by neurologists/epileptologists. The reliability of the responses is determined with the inter-rater intraclass correlation coefficient (ICC). If the ICC is not large enough the Spearman-Brown prophecy formula can be used to predict the number of additional experts. We propose a method to assess whether an additional expert provides information consistent with the already acquired data as well as a method to detect experts with deviating opinions. The power of the first method was determined.

Results:
Data were collected for five seizure types. The ICCs determined from the responses for the various seizure types after inclusion of the additional experts was in all cases almost equal to 0.9, the target value. Yet one expert with diverging opinions concerning the frequency of occurrence of manifestations for different seizure types could be identified. Excluding this participant improved the reliability of the data. The power of the methods was good (≥ 0.75).

Conclusions:
It is shown that human experts can provide reliable information about the frequency of occurrence of manifestations in epileptic seizures. In addition, the described approach correctly identified neurologists/epileptologists with both consistent and diverging opinions about the frequency of occurrence of manifestations in a number of seizure types.
Intensity-based Image Registration with a Guaranteed One-to-one Point Match
Authors: Modersitzki J. , Fischer B.
Published: March 2018

Objectives:
In this paper, we propose a novel registration technique, which combines the concepts of landmark and automatic, non-rigid intensity-based approaches. A general framework, which might be used for many different registration problems is presented. The novel approach enables the incorporation of different distance measures as well as different smoothers.

Methods:
The proposed scheme minimizes a regular-ized distance measure subject to some interpolation constraints. The desired deformation is computed iteratively using an Euler-scheme for the first variation of the chosen objective functional.

Results:
A fast and robust numerical scheme for the computation of the wanted minimizer is developed, implemented, and applied to various registration tasks. This includes the registration of pre- and post-intervention images of the human eye.

Conclusions:
A novel framework for a parameter-free, non-rigid registration scheme which allows for the additional incorporation of user-defined landmarks is proposed. It enhances the reliability of conventional approaches considerably and thereby their acceptability by practitioners in a clinical environment.
A Semantic Approach to Segmentation of Overlapping Objects
Authors: Grobe M. , Münzenmayer C. , Kuziela H. , Spinnler K. , Wittenberg T.
Published: March 2018

Objectives:
This paper aims at introducing a novel approach for segmentation of overlapping objects and at demonstrating its applicability to medical images.

Methods:
This work details a novel approach enhancing the known theory of full-segmentation of an image into regions by lifting it to a semantic segmentation into objects. Our theory allows the formal description of partitioning an image into regions on the first level and allowing the occurrence of overlaps and occlusions of objects on a second, semantic level. Possible applications for the use of this ‘semantical segmentation‘ are the analysis of radiographs and micrographs. We demonstrate our approach by the example of segmentation and separation of overlapping cervical cells and cell clusters on a set of 787 image pairs of registered PAP- and DAPI-stained micrographs. The semantical cell segmentation yielding areas of cell plasmas and nuclei are compared to a manual segmentation of the same images, where 2212 cells have been labeled. A direct comparison of over and under-segmentation between the two segmentation sets yields a mean difference value of 10.15% for the nuclei and 10.80% for the plasma.

Results:
Using the proposed theory of semantical segmentation of images in combination with adequate models of the image contents, our approach allows identifying, separating and distinguishing several overlapping, occluding objects in medical images. Applying the proposed theory to the application of cervical cell segmentation from overlapping cell clusters and aggregates, it can be seen that it is possible to formally describe the complex image contents.

Conclusions:
The proposed method of semantical segmentation is a mighty tool and under the assumption of the subtractive transparency model can be used in different medical image processing applications such as radiology and microscopy. By using alternative models to solve the ambiguities attached to overlaps and occlusions, further fields of application can be addressed.
Comparison of Preprocessing Procedures for Oligo-nucleotide Micro-arrays by Parametric Bootstrap Simulation of Spike-in Experiments
Authors: Freudenberg J. , Boriss H. , Hasenclever D.
Published: March 2018

Objective:
Due to scarcity of calibration data for micro-array experiments, simulation methods are employed to assess preprocessing procedures. Here we analyze several procedures’ robustness against increasing numbers of differentially expressed genes and varying proportions of up-regulation.

Methods:
Raw probe data from oligo-nucleotide micro-arrays are assumed to be approximately multivariate normally distributed on the log scale. Chips can be simulated from a multivariate normal distribution with mean and variance-covariance matrix estimated from a real raw data set.

A chip effect induces strong positive correlations. In reverse, sampling from a normal distribution with strong correlation variance-covariance matrix generates data exhibiting a chip effect. No explicit model of chip-effect is needed. Differences can be artificially spiked-in according to a given distribution of effect sizes.

Thirty preprocessing procedures combining background correction, normalization, perfect match correction and summarization methods available from the BioConductor project were compared.

Results:
In the symmetrical setting “50% differentially expressed genes, 50% of which up-regulated” background correction reduces bias, but inflates low intensity probe variance as well as the mean squared error of the estimates. Any normalization reduces variance and increases sensitivity with no clear winner. Asymmetry between up and down regulation causes bias in the effect-size estimate of non-differentially expressed genes. This markedly inflates the false positive discovery rates. Variance stabilizing normalization (VSN) behaved best.

Conclusion:
A simple parametric bootstrap was used to simulate oligo-nucleotide micro-array raw data. Current normalization methods inflate the false positive rate when many genes show an effect in the same direction.
Correcting the QT Interval for Changes in HR in Pre-clinical Drug Development
Authors: Markert M. , Meyners M.
Published: March 2018

Objectives:
Estimation of possible cardiovascular side effects belongs to the safety assessment of every drug candidate. Drug-induced prolongation of the QT interval can result in life-threatening ventricular arrhythmia. In pre-clinical drug development, animal experiments are used to study this possible effect. Researchers have become aware that correction formulae derived for human beings are not applicable to animal experiments.

Methods:
We investigated some of the proposed models by comparing the outcomes of the analyses on the same data. The data was derived from telemetry measurements on Labrador dogs. We propose the use of both the correlation with heart rate (or RR interval) and a measure of predictive performance. As a sufficiently large number of observations were available, the data was subdivided into a training and a test set. The training set serves to estimate the respective parameters while the test set is used to determine the performance of the model. Here, a kind of PRESS statistic was used. Next, the models were considered for treated animals, using the estimated parameters. Both positive and negative controls were used.

Conclusions:
Most models under consideration performed quite well. These models eliminated the correlation for the most part and were reasonably predictive. Furthermore, they reliably differentiate between positive and negative controls. The next steps in identifying the best correction will be to consider additional compounds as well as other species to validate our current results.
Simultaneous Confidence Intervals for Ratios with Applications to the Comparison of Several Treatments with a Control
Authors: Bretz F. , Guiard V. , Hothorn L. A. , Dilba G.
Published: March 2018

Objectives:
In this article, we illustrate and compare exact simultaneous confidence sets with various approximate simultaneous confidence intervals for multiple ratios as applied to many-to-one comparisons. Quite different datasets are analyzed to clarify the points.

Methods:
The methods are based on existing probability inequalities (e.g., Bonferroni, Slepian and Šidàk), estimation of nuisance parameters and re-sampling techniques. Exact simultaneous confidence sets based on the multivariate t-distribution are constructed and compared with approximate simultaneous confidence intervals.

Results:
It is found that the coverage probabilities associated with the various methods of constructing simultaneous confidence intervals (for ratios) in many-to-one comparisons depend on the ratios of the coefficient of variation for the mean of the control group to the coefficient of variation for the mean of the treatments. If the ratios of the coefficients of variations are less than one, the Bonferroni corrected Fieller confidence intervals have almost the same coverage probability as the exact simultaneous confidence sets. Otherwise, the use of Bonferroni intervals leads to conservative results.

Conclusions:
When the ratio of the coefficient of variation for the mean of the control group to the coefficient of variation for the mean of the treatments are greater than one (e.g., in balanced designs with increasing effects), the Bonferroni simultaneous confidence intervals are too conservative. Therefore, we recommend not using Bonferroni for this kind of data. On the other hand, the plug-in method maintains the intended confidence coefficient quite satisfactorily; therefore, it can serve as the best alternative in any case.
Some Problems with the Investigation of Noninferiority in Meta-analysis
Authors: Victor N. , Witte S.
Published: March 2018

Objectives:
Noninferiority trials have become commonplace in recent years. Like individual clinical trials, meta-analyses can also investigate noninferiority. However, certain important topics have to be considered.

Methods:
The proposed methods in this paper have their origin in the framework of noninferiority trials and meta-analyses. This paper can therefore be seen as a combination of both fields. Two issues are highlighted in the paper; difficulties in the choice of delta for a noninferiority meta-analysis leading to different deltas and methods for meta-analyses with different analysis sets, based on the full-analysis set with the intention-to-treat principle or the per-protocol population. Analytical methods, sensitivity analyses, meta-regression, and a bivariate method are introduced. The proposed graphical presentations support the analytical results.

Conclusion:
The confidence interval approach using meta-regression or bivariate methods is appropriate using both analysis sets for meta-analyses investigating noninferiority.
Determination of the Population Size
in an Epidemiological Study with Children
Authors: Forster J. , Petersen G. , Schumacher M. , Ihorst G.
Published: March 2018

Objectives:
To obtain a reliable estimate of the population size in an epidemiological study concerned with incidence estimation.

Methods:
In the present case, the population of interest consists of all children attending a certain pediatric practice for any reason and is estimated making use of the number of regularly attended well baby visits. In some cases, exact figures from the practices are available as a reference. A prospective epidemiological study on the estimation of the incidence of lower respiratory tract infections (LRTI) in the German pediatric population (PRI.DE, Parainfluenza- und Respiratory-Syncytial-Virus-Infektionen in Deutschland) is used to demonstrate the procedure.

Results:
In most cases, the fit can be regarded as good with deviations between 11% and 17%, whereas in a few cases it must be considered as poor (deviations of 60%).

Conclusions:
The importance of using exact figures whenever obtainable and of appraising the results carefully is emphasized.