Christian M. Zechmann

3D printing based on imaging data: review of medical applications

PurposeGeneration of graspable three-dimensional objects applied for surgical planning, prosthetics and related applications using 3D printing or rapid prototyping is summarized and evaluated.Materials and methodsGraspable 3D objects overcome the limitations of 3D visualizations which can only be displayed on flat screens. 3D objects can be produced based on CT or MRI volumetric medical images. Using dedicated post-processing algorithms, a spatial model can be extracted from image data sets and exported to machine-readable data. That spatial model data is utilized by special printers for generating the final rapid prototype model.ResultsPatient–clinician interaction, surgical training, medical research and education may require graspable 3D objects. The limitations of rapid prototyping include cost and complexity, as well as the need for specialized equipment and consumables such as photoresist resins.ConclusionsMedical application of rapid prototyping is feasible for specialized surgical planning and prosthetics applications and has significant potential for development of new medical applications.

Anterior cruciate ligament reconstruction using patellar tendon versus hamstring tendon: a prospective comparative study with 9-year follow-up.

PURPOSE To analyze the long-term evaluation of clinical, functional, and magnetic resonance imaging (MRI) results after implant-free press-fit anterior cruciate ligament (ACL) reconstruction with bone-patella tendon (BPT) versus quadrupled hamstring tendon (HT) grafts. METHODS Sixty-two ACL-insufficient patients were included in a prospective, randomized study (31 BPT and 31 HT). Both surgical procedures were performed without any implants by a press-fit technique by the senior author. The femoral tunnel was drilled through the anteromedial portal for anatomic placement. At 8.8 years after reconstruction, 53 patients (28 BPT and 25 HT) were examined by different clinical and functional tests. Bilateral MRI scans were performed and interpreted by an independent radiologist. RESULTS On follow-up, the score on the International Knee Documentation Committee evaluation form was significantly better in the HT group. The clinical examination including range of motion, KT-1000 test (MEDmetric, San Diego, CA), and pivot-shift test showed no significant differences. On isokinetic testing, the mean quadriceps strength was close to normal (96%) in both groups, but the hamstring strength was lower in the HT group (100.3%/95.1%). Kneeling (1.5/1.1, P = .002), knee walking (1.72/1.14, P = .002), and single-leg hop test (95.8%/99.1%, P = .057) were better in the HT group. The MRI findings about the mean degree of cartilage lesion (International Cartilage Repair Society protocol) of the operated (2.1/2.1) and nonoperated (1.4/1.8) knee showed no significant differences. No significant difference was found in the grade of medial or lateral meniscal lesion or the number of patients having meniscal lesions when the operated and nonoperated knees were compared. Tunnel measurements, Caton-Deschamps Index, and the sagittal ACL angle were similar. CONCLUSIONS The implant-free press-fit technique for anterior cruciate ligament reconstruction by use of bone-patellar tendon and hamstring grafts with anatomic graft placement is an innovative technique to preserve the cartilage and meniscal status without significant differences between the operated and nonoperated knees in the long term. Significantly less anterior knee pain was noted in the hamstring group, when testing for kneeling and knee walking. LEVEL OF EVIDENCE Level II, prospective comparative study.

Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: A comparative study with histology

Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion‐weighted imaging (DWI) is a magnetic resonance imaging‐technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI‐parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro‐vessel density (P < 0·001 respectively). ADC was significantly different between patients and controls (P < 0·01) and before and after systemic therapy (P < 0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non‐invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work‐up to assess tumour burden.

Lumbar Bone Marrow Microcirculation Measurements from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Is a Predictor of Event-Free Survival in Progressive Multiple Myeloma

Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with high temporal resolution enables the detection of microcirculation variables amplitude A and exchange rate constant kep. In this study, the prognostic value of the DCE-MRI variables for overall survival and event-free survival in patients with progressive multiple myeloma was investigated. Experimental Design: Between 1999 and 2001, 65 patients with progressive or relapse of multiple myeloma requiring therapy were investigated with DCE-MRI of the lumbar spine before start of therapy. The contrast uptake was quantified using a two-compartment model with the output variables amplitude A and exchange rate constant kep reflecting bone marrow microcirculation. The estimated median follow-up was 56 months. Event-free survival and overall survival were investigated for DCE-MRI variables and for established prognosis variables (β2-microglobulin, lactate dehydrogenase, albumin, and age). Results: Using a multivariate Cox regression model, β2-microglobulin and amplitude A of DCE-MRI were identified as statistically significant prognostic variable of event-free survival with Ps of 0.01 and 0.02, respectively. A statistical correlation of DCE-MRI variables with overall survival could not be found. The multivariate analysis of β2-microglobulin, age, lactate dehydrogenase, and albumin revealed β2-microglobulin as statistically significant prognostic factor for overall survival in this group of patients (P < 0.001). Conclusions: This analysis identifies contrast-enhanced DCE-MRI variable amplitude A reflecting increased bone marrow microcirculation and angiogenesis as a novel and possibly useful prognostic factor in patients with multiple myeloma. Prospective studies are currently done to further investigate this functional variable for prognosis and stratification of myeloma patients.

Discriminating cancer from noncancer tissue in the prostate by 3-dimensional proton magnetic resonance spectroscopic imaging: a prospective multicenter validation study.

Objectives:A prospective multicenter validation of the ability of 1H magnetic resonance spectroscopic imaging (MRSI) to distinguish cancer from noncancer tissues throughout the prostate with histopathology of the resected organ as the standard of reference. Materials and Methods:Institutional review board approval was obtained for all centers and all participating patients and volunteers provided written informed consent. Ninety-nine patients and 10 age-matched volunteers from 8 participating centers underwent magnetic resonance imaging and 3-dimensional MRSI with an endorectal coil at 1.5 T. Selected MRSI voxels were assigned to the peripheral zone (PZ), the central gland (CG), the periurethral area, and cancer tissue. Signal ratios of choline + creatine to citrate (CC/C) in spectra of these voxels were automatically calculated. Receiver operating characteristic curves were constructed to assess the accuracy by which this ratio can discriminate cancer from noncancer tissue. Results:A total of 70% of voxels in noncancer tissue and 90% of voxels in cancer tissue passed the quality check of the automatically fitted spectra. The median CC/C was significantly different between any noncancer and cancer tissue (P < 0.0001), but not between the different contributing centers. CC/C increased with cancer focus size (P = 0.0008) and certainty of voxel mapping to histopathologic cancer site (P < 0.0001). The area under the receiver operating characteristic curve for discriminating voxels of cancer tissue from noncancer tissue was 0.88 (confidence interval: 0.84–0.92) in the PZ and 0.76 (confidence interval: 0.71–0.81) in the CG. Conclusions:In patients with prostate cancer, recruited from different institutions, 3-dimensional MRSI is demonstrated to be a robust and quantitative technique, producing significantly different CC/C values for cancer compared with noncancer tissue for both the CG and the PZ.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Purpose: The aim of our study was to investigate whether dynamic contrast–enhanced magnetic resonance imaging (DCE-MRI) allows visualization of changes in microcirculation between healthy controls on the one side and early/advanced stages of plasma cell disease on the other. Experimental Design: We examined a group of 222 individuals consisting of 60 patients with monoclonal gammopathy of undetermined significance (MGUS), 65 patients with asymptomatic multiple myeloma (aMM), 75 patients with newly diagnosed symptomatic MM (sMM), and 22 healthy controls with DCE-MRI of the lumbar spine. Results: A continuous increase in microcirculation parameters amplitude A and exchange rate constant kep reflecting vascular volume and permeability, respectively, was detected from normal controls over MGUS and aMM to sMM. For A and kep, significant differences were found between controls and aMM (P = 0.03 and P = 0.004, respectively) as well as controls and sMM (P = 0.001 and P < 0.001, respectively). Although diffuse microcirculation patterns were found in healthy controls as well as MGUS and MM, a pattern with focal hotspots was exclusively detected in 42.6% of sMM and in 3 MGUS and 3 aMM patients. MGUS and aMM patients with increased microcirculation patterns showed significantly higher bone marrow plasmocytosis compared with patients with a low microcirculation pattern. Conclusions: Our investigations substantiate the concept of an angiogenic switch from early plasma cell disorders to sMM. Pathologic DCE-MRI findings correlate with adverse prognostic factors and DCE-MRI identifies a distinct group of patients with increased microcirculation parameters in aMM and MGUS patients.

Multicenter, Double-Blind, Randomized, Intraindividual Crossover Comparison of Gadobenate Dimeglumine and Gadopentetate Dimeglumine for Breast MR Imaging (DETECT Trial)

PURPOSE To intraindividually compare 0.1 mmol/kg doses of gadobenate dimeglumine and gadopentetate dimeglumine for contrast material-enhanced breast magnetic resonance (MR) imaging by using a prospective, multicenter double-blind, randomized protocol. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. One hundred sixty-two women (mean age, 52.8 years ± 12.3 [standard deviation]) enrolled at 17 sites in Europe and China between July 2007 and May 2009 underwent at least one breast MR imaging examination at 1.5 T by using three-dimensional spoiled gradient-echo sequences. Of these, 151 women received both contrast agents in randomized order in otherwise identical examinations separated by more than 2 but less than 7 days. Images, acquired at 2-minute or shorter intervals after contrast agent injection, were evaluated independently by three blinded radiologists unaffiliated with enrollment centers. Histopathologic confirmation was available for all malignant lesions (n = 144), while benign lesions were confirmed either by using histopathologic examination (n = 52) or by at least 12-month diagnostic follow-up (n = 20) with mammography and/or ultrasonography. Determinations of malignant lesion detection rates and diagnostic performance (sensitivity, specificity, accuracy, positive predictive value [PPV], and negative predictive value [NPV]) were performed and compared (McNemar and Wald tests). A full safety assessment was performed. RESULTS Significant superiority for gadobenate dimeglumine was noted by readers 1, 2, and 3 for malignant lesion detection rate (91.7%, 93.1%, 94.4% vs 79.9%, 80.6%, 83.3%, respectively; P ≤ .0003). Readers 1, 2, and 3 reported significantly superior diagnostic performance (sensitivity, specificity, and accuracy) for breast cancer detection with gadobenate dimeglumine (91.1%, 94.5%, 95.2% vs 81.2%, 82.6%, 84.6%; 99.0%, 98.2%, 96.9% vs 97.8%, 96.9%, 93.8%; 98.2%, 97.8%, 96.7% vs 96.1%, 95.4%, 92.8%, respectively; P ≤ .0094) and significantly superior PPV (91.1%, 85.2%, 77.2% vs 80.7%, 75.5%, 60.9%, respectively; P ≤ .0002) and NPV (99.0%, 99.4%, 99.4% vs 97.8%, 98.0%, 98.1%, respectively; P ≤ .0003). No safety concerns were noted with either agent. CONCLUSION Gadobenate dimeglumine is superior to gadopentetate dimeglumine for breast cancer diagnosis.

Automated estimation of tumor probability in prostate magnetic resonance spectroscopic imaging: pattern recognition vs quantification.

Despite its diagnostic value and technological availability, 1H NMR spectroscopic imaging (MRSI) has not found its way into clinical routine yet. Prerequisite for the clinical application is an automated and reliable method for the diagnostic evaluation of MRS images. In the present paper, different approaches to the estimation of tumor probability from MRSI in the prostate are assessed. Two approaches to feature extraction are compared: quantification (VARPRO, AMARES, QUEST) and subspace methods on spectral patterns (principal components, independent components, nonnegative matrix factorization, partial least squares). Linear as well as nonlinear classifiers (support vector machines, Gaussian processes, random forests) are applied and discussed. Quantification‐based approaches are much more sensitive to the choice and parameterization of the quantification algorithm than to the choice of the classifier. Furthermore, linear methods based on magnitude spectra easily achieve equal performance and also allow for biochemical interpretation in combination with subspace methods. Nonlinear methods operating directly on magnitude spectra achieve the best results but are less transparent than the linear methods. Magn Reson Med 57:150–159, 2007.

Estimating Kinetic Parameter Maps From Dynamic Contrast-Enhanced MRI Using Spatial Prior Knowledge

Dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging can be used to study microvascular structure in vivo by monitoring the abundance of an injected diffusible contrast agent over time. The resulting spatially resolved intensity-time curves are usually interpreted in terms of kinetic parameters obtained by fitting a pharmacokinetic model to the observed data. Least squares estimates of the highly nonlinear model parameters, however, can exhibit high variance and can be severely biased. As a remedy, we bring to bear spatial prior knowledge by means of a generalized Gaussian Markov random field (GGMRF). By using information from neighboring voxels and computing the maximum a posteriori solution for entire parameter maps at once, both bias and variance of the parameter estimates can be reduced thus leading to smaller root mean square error (RMSE). Since the number of variables gets very big for common image resolutions, sparse solvers have to be employed. To this end, we propose a generalized iterated conditional modes (ICM) algorithm operating on blocks instead of sites which is shown to converge considerably faster than the conventional ICM algorithm. Results on simulated DCE-MR images show a clear reduction of RMSE and variance as well as, in some cases, reduced estimation bias. The mean residual bias (MRB) is reduced on the simulated data as well as for all 37 patients of a prostate DCE-MRI dataset. Using the proposed algorithm, average computation times only increase by a factor of 1.18 (871 ms per voxel) for a Gaussian prior and 1.51 (1.12 s per voxel) for an edge-preserving prior compared to the single voxel approach (740 ms per voxel).

Pharmacokinetic Analysis of Malignant Pleural Mesothelioma—Initial Results of Tumor Microcirculation and its Correlation to Microvessel Density (CD-34)

RATIONALE AND OBJECTIVES Malignant mesothelioma (MM) of the pleura is an aggressive and often fatal neoplasm. Because MM frequently demonstrates marked angiogenesis, it may be responsive to antiangiogenic therapy, but effective methods for selecting and monitoring of patients are further needed. We employed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative immunohistochemistry (IHC) to characterize the microvascularity of MM using both a physiologic and ultrastructural method. MATERIALS AND METHODS Nineteen patients diagnosed with MM were enrolled and DCE-MRI was performed before antiangiogenic treatment. For each patient, tumor regions were characterized by their DCE-MRI-derived pharmacokinetic parameters (Amp, k(ep), k(el)), which were also compared to those of normal tissue (aorta, liver, spleen, and muscle). In addition, quantitative IHC of representative samples was performed with CD-34 staining to compare the calculated microvessel density (MVD) results with DCE-MRI results. RESULTS MM demonstrated markedly abnormal pharmacokinetic properties compared with normal tissues. Among the parameters tested, Amp was significantly different in MM (P < or = .001) compared to normal organs. Despite the observation that the MVD of mesotheliomas in this series was high compared to other tumors, DCE-MRI pharmacokinetic parameters had a moderately positive correlation with MVD (r = 0.5). CONCLUSIONS DCE-MRI and IHC can be used in patients with MM to visualize tumor microvascularity and to characterize tumor heterogeneity. DCE-MRI and IHC results positively correlated, though moderately, but these two methods present as essential tumor biomarkers. This multimodal characterization may be useful in selecting possible tumor subtypes that would benefit from antiangiogenic therapy.