Search Results (31)

Background/Objectives: This study investigates the utility of multiparametric PET/MRI in delineating changes in physiologically distinct intratumoral habitats during trastuzumab-induced alterations in a preclinical HER2+ breast cancer model. Methods: By integrating diffusion-weighted MRI, dynamic contrast-enhanced MRI, [¹⁸F]Fluorodeoxyglucose- and [¹⁸F]Fluorothymidine-PET, voxel-wise parametric maps were generated capturing cellular density, vascularity, metabolism, and proliferation. BT-474 tumor-bearing mice have high expression of HER2 and, in response to trastuzumab, an anti-HER2 antibody, effectively show changes in proliferation and tumor microenvironment alterations that result in decreases in tumor volume through time. Results: Single imaging metrics and changes in metrics were incapable of identifying treatment-induced alterations early in the course of therapy (day 4) prior to changes in tumor volume. Hierarchical clustering identified five distinct tumor habitats, which enabled longitudinal assessment of early treatment response. Tumor habitats were defined based on imaging metrics related to biology and categorized as highly vascular (HV), hypoxic responding (HRSP), transitional zone (TZ), active tumor (ATMR) and responding (RSP). The HRSP cluster volume significantly decreased in trastuzumab-treated tumors compared to controls by day 4 (p = 0.015). The volume of ATMR cluster was significantly different at baseline between cohorts (p = 0.03). The TZ cluster, indicative of regions transitioning more to necrosis, significantly decreased in treated tumors (p = 0.031), suggesting regions had already transitioned. Multiparametric image clustering showed a significant positive linear correlation with histological multiparametric mapping, with R² values of 0.56 (HRSP, p = 0.013, 0.64 (ATMR, p = 0.0055), and 0.49 (responding cluster, p = 0.024), confirming the biological relevance of imaging-derived clusters. Conclusions: These findings highlight the potential utility of multiparametric PET/MRI to capture biological alterations prior to any single imaging metric which has potential for better understanding longitudinal changes in biology, stratifying tumors based on those changes, optimizing therapeutic monitoring and advancing precision oncology. Full article

Quadriceps tendon tears are uncommon lesions and their diagnosis can be missed in up to 50% of cases. We report a case of a 83-year-old man with polio who has a chronic quadriceps tendon tear in a healthy limb. A modified Codivilla technique augmented with an ipsilateral semitendinosus tendon was performed. Partial weight bearing was allowed immediately after surgery, and at 3 months the patient was able to walk with full weight bearing on the involved limb. The 5-year follow-up MRI showed good quadriceps tendon healing with the full integration of the tendon graft. Tendon repair with autograft augmentation represents a potential and effective solution in elderly patients with a chronic quadriceps tendon tear. Full article

Background and Objectives: Osteoporosis is becoming more prevalent with the rise in the aging population, leading to the increased use of bisphosphonates for treatment. While these medications are effective in preventing osteoporotic fractures, long-term use has been associated with atypical insufficiency fractures, primarily in the femur. However, atypical fractures in other weight-bearing bones, such as the tibia, have rarely been reported. This study aims to present a case of an atypical insufficiency fracture of the tibia in an elderly female who has been on long-term bisphosphonate therapy and to review treatment outcomes within the context of the current literature. Patient concerns: A 76-year-old female presented with pain in the proximal right tibia, developing two months prior without trauma. She had been receiving long-term bisphosphonate therapy for osteoporosis, initially taking sodium risedronate orally for 4 years, followed by intravenous ibandronate for 10 years. Physical examination revealed localized tenderness, and radiographs showed cortical thickening and a horizontal fracture line in the proximal right tibia. MRI confirmed these findings, along with surrounding edema. The laboratory results were mostly normal, but the bone formation marker osteocalcin was significantly reduced. The patient had a history of insufficiency fractures in the ipsilateral tibia and contralateral femur, previously treated conservatively with teriparatide. A similar conservative approach was attempted but failed, leading to surgical intervention with intramedullary nailing and supplementary plating. At the 8-month follow-up, the patient showed successful fracture union and resolution of symptoms. Conclusion: Long-term use of bisphosphonates, though effective for osteoporosis, can lead to atypical insufficiency fractures, primarily in the femur but also occasionally in the tibia. Clinicians should consider this possibility when patients present with pain in weight-bearing bones without a history of trauma. Prompt diagnosis through thorough history-taking, physical examination, and appropriate imaging is essential to ensure timely management. Full article

Talar avascular necrosis (AVN) is a devastating condition that frequently follows type III and IV talar neck fractures. As 60% of the talus is covered by hyaline cartilage, its vascular supply is limited and prone to trauma, which may eventually lead to AVN development. Early detection of AVN (Hawkins sign, MRI) is crucial, as it may prevent the development of the irreversible stages III and IV of AVN. Alertness is advised regarding non-obvious conditions that may cause this complication (sub chondroplasty, systemic lupus erythematosus, diabetes mellitus). Although, in stages I–II, AVN may be treated with non-surgical procedures (ESWT therapy, non-weight bearing) or joint-sparing techniques (core drilling, bone marrow aspirate injections), stages III–IV require more advanced procedures, such as joint-sacrificing procedures (hindfoot arthrodesis/ankle arthrodesis), or replacement surgery, including total talar replacement (TTR) or combined total ankle replacement (TAR). The advancement of 3D-printing technology and increased access to implant manufacturing are contributing to a rise in the production rates of third-generation total talar prostheses. As a result, there is a growing frequency of alloplasty procedures and combined total ankle replacement (TAR) surgeries. By performing TTR as opposed to deses, the operator avoids (i) delayed union, (ii) a shortening of the limb, (iii) a lack of mobility, and (iv) the stiffening of adjacent joints, which are the main disadvantages of joint-sacrificing procedures. Simultaneously, TTR and combined TAR offer (i) a brief period of weight-bearing restriction, (ii) quick pain relief, and (iii) preservation of the length of the limb. Here, we summarize the most up-to-date knowledge regarding AVN diagnosis and treatment, with a special focus on the role of TTR. Full article

Evaluating intratumor heterogeneity with image texture analysis offers a more sophisticated understanding of sarcoma response to treatment. We examined the effects of inductive moderate hyperthermia (IMH) on sarcoma-45 growth and intratumor heterogeneity across tissue, cellular and molecular levels using magnetic resonance imaging (MRI), ultrasound and histology image analysis. IMH (42 MHz, 20 W) inhibited sarcoma-45 growth kinetics by 34% compared to the untreated control group. T₂-weighted MRI brightness was increased by 42%, reflecting more extensive tumor necrosis, while Young’s modulus increased by 37% due to more pronounced connective tissue replacement in response to IMH. Whereas calculations of Moran’s spatial autocorrelation index revealed distinctions in heterogeneity between tumor core, periphery and capsule regions of interest (ROIs) on MRI, ultrasound and histological examination in the untreated tumor-bearing animals, there was no significant difference between core and periphery after IMH. Exposure to IMH increased overall tumor ROI heterogeneity by 22% on MRI but reduced heterogeneity in the core and periphery on ultrasound and histology images. Ki-67 protein distribution was 25% less heterogeneous on the tumor periphery after IMH. Therefore, this study provides a quantitative characterization of IMH effects on different manifestations of intratumor sarcoma-45 heterogeneity using experimental imaging data. Full article

Background: The diagnosis of anterior cruciate ligament (ACL) tear relies on clinical evaluation and magnetic resonance imaging (MRI). Direct and indirect signs of ACL tear have been described with MRI evaluation. Posterior cruciate ligament (PCL) buckling has been described as an indirect radiographic sign of an ACL tear. Purpose: The aim of the present study was to assess the variations in PCL buckling angles in patients with ACL tears and in patients with isolated lesions in the posterior horn of the medial meniscus. In addition, the influence of different patterns of medial meniscus tears in ACL-deficient knees was investigated. Finally, the influences of risk factors such as tibial slope, delay from injury to surgery, absence of medial meniscus tear, degree of Lachman and pivot shift testing were also assessed. Study design: This was a cohort study. Methods: A total of 154 patients (78 in the group with ACL tear and 76 in the control group) were assessed with MRI and lateral weight-bearing X-ray to assess PCL buckling angle and tibial slope by two independent observers. The presence of a medial meniscus bucket handle or ramp lesion of the medial meniscus was assessed and recorded at the time of surgery. Results: PCL buckling angle measurement was highly reliable, with an ICC of 0.866 and 0.894, respectively, in the study group and the control group for interobserver reliability. The intrarater reliability was found to be high in PCL buckling angle for the study group [ICC = 0.955] and the control group [ICC = 0.943]. The mean angle in patients with ACL tear was 110.7 ± 15.2° and 115.3 ± 16.2° (for the two examiners) and 111.4 ± 12° and 114 ± 14.5° (for the two examiners) in patients with an intact, healthy ACL. An association emerged between bucket handle tears of the medial meniscus (p = 0.010) and a decreased PCL buckling angle and between ramp lesions of the medial meniscus and increased PCL buckling angle both (p = 0.024). Conclusions: Good inter- and intraobserver reliability for the measurement of the PCL buckling angle was observed. Increased PCL buckling angle values were observed in patients with concomitant ACL and bucket handle tears of the medial meniscus, while decreased angle values were observed in those who had ACL tear and ramp lesion of the medial meniscus. No statistically significant difference in the PCL buckling angle emerged between patients with ACL tears and those who had a healthy, intact ACL. Full article

Knee injuries, particularly anterior cruciate ligament (ACL) damage and cartilage defects, are highly prevalent among athletes and affect their sports performance and long-term joint function. The purpose of this research was to evaluate the effectiveness of a comprehensive combination therapy approach for individuals with ACL and cartilage injuries. Twelve professional soccer players aged 18 to 30 years underwent bone–tendon–bone ACL reconstruction, microfracture cartilage repair surgery, and hyaluronic acid scaffold treatment. Early postoperative rehabilitation included immediate supervised physiotherapy and complete weight bearing. Follow-up assessments involved clinical evaluations, functional joint assessments, and magnetic resonance imaging (MRI) scans to measure cartilage defect repair and symptom alleviation. The results showed that patients resumed pain-free activities within 3–4 weeks and returned to their pre-injury level within 4.5 months. MRI demonstrated the absence of inflammatory reactions, repair of marrow edema, and the emergence of new cartilage. Six months and one year after surgery, the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Short Form (36) Health Survey (SF-36) questionnaire results demonstrated considerable improvement in patients’ health condition and quality of life. Overall, the study suggests that the combination of Hyalofast membranes, microfracture surgery, tissue adhesive, and intensive postoperative physical therapy may be a potential alternative to commonly used treatments for patients with ACL rupture, allowing them to recover efficiently and return to sports activities. Full article

The purpose of this prospective case series was to determine the effectiveness of using a combination of the core decompression and injection of autologous conditioned plasma (ACP) for the treatment of symptomatic knee bone marrow lesions (BML), as well as to report on the preliminary clinical results based on magnetic resonance imaging (MRI) and patient-reported outcomes (PROMs). Patients with OA-related BML who failed to improve on conservative treatment for three months underwent an identical procedure consisting of arthroscopy, core decompression, and the intraosseous injection of ACP and were followed up for 12 months. A statistically significant reduction in pain and an improvement in function, as measured by the Numeric Pain Rating Scale (NPRS) and Knee Injury and Osteoarthritis Outcome Score (KOOS), was observed at one-week follow-up (8.3 ± 0.8 to 1.5 ± 1.0; p ≤ 0.001 and 33.4 ± 10.6 to 53.9 ± 13.6; p ≤ 0.001 respectively). After six weeks, weight-bearing was allowed, but the trend did not change—the NPRS continued to be low (average 1.4 on 12-month follow-up) and the total KOOS increased 44.6 points from the baseline (average 78.0 on 12-month follow-up). The Whole-Organ Magnetic Resonance Imaging Score improved from 66.1 ± 19.4 prior to surgery to 58.0 ± 15.9 (p < 0.001) after 3 months. In our study, there was no control group, randomisation was not performed, and the sample size was relatively small. A combination of core decompression and the intraosseous injection of ACP into the affected subchondral area proved to be a safe and effective procedure that provides rapid pain relief and a significant increase in joint function up to one year postoperatively. Full article

The application of many currently evaluated macromolecular contrast agents for magnetic resonance imaging (MRI) has been limited because of their bio-incompatibility and toxicity. The aim of this study is to synthesize and characterize a new micelle-based TPGS gadolinium chelate as a biocompatible MRI contrast agent for prolonged blood circulation time and good tumor imaging contrast. The TPGS-gadolinium conjugate was prepared through the conjugation between TPGS-SA and bifunctional L-NETA-Gd chelate. The conjugate was characterized with regard to molecular weight, critical micellar concentration and particle sizes, cellular uptake, and in vitro cell MRI. Distributions of the MRI contrast agent in various organs were determined via intravenous injection of the agent into mice bearing xenograft tumors. The successfully prepared TPGS-L-NETA-Gd micelle exhibited improved cellular uptake in HepG2 cells and xenografts and high in vivo safety. Distributions of TPGS-L-NETA-Gd in mice showed enhanced cellular uptake up to 2 h after the contrast agent injection. Its in vitro and in vivo properties make it a favorable macromolecular MRI contrast agent for future in vivo imaging. Full article

Adult acquired flatfoot deformity (AAFD) is a disorder caused by repetitive overloading, which leads to progressive posterior tibialis tendon (PTT) insufficiency. It mainly affects middle-aged women and occurs with foot pain, malalignment, and loss of function. After clinical examination, imaging plays a key role in the diagnosis and management of this pathology. Imaging allows confirmation of the diagnosis, monitoring of the disorder, outcome assessment and complication identification. Weight-bearing radiography of the foot and ankle are gold standard for the diagnosis of AAFD. Magnetic Resonance Imaging (MRI) is not routinely needed for the diagnosis; however, it can be used to evaluate the spring ligament and the degree of PTT damage which can help to guide surgical plans and management in patients with severe deformity. Ultrasonography (US) can be considered another helpful tool to evaluate the condition of the PTT and other soft-tissue structures. Computed Tomography (CT) provides enhanced, detailed visualization of the hindfoot, and it is useful both in the evaluation of bone abnormalities and in the accurate evaluation of measurements useful for diagnosis and post-surgical follow-up. Other state-of-the-art imaging examinations, like multiplanar weight-bearing imaging, are emerging as techniques for diagnosis and preoperative planning but are not yet standardized and their scope of application is not yet well defined. The aim of this review, performed through Pubmed and Web of Science databases, was to analyze the literature relating to the role of imaging in the diagnosis and treatment of AAFD. Full article

The in-vivo quantification of knee motion in physiological loading conditions is paramount for the understanding of the joint’s natural behavior and the comprehension of articular disorders. Dynamic MRI (DMRI) represents an emerging technology that makes it possible to investigate the functional interaction among all the joint tissues without risks for the patient. However, traditional MRI scanners normally offer a reduced space of motion, and complex apparatus are needed to load the articulation, due to the horizontal orientation of the scanning bed. In this study, we present an experimental and computational procedure that combines an open, weight-bearing MRI scanner with an original registration algorithm to reconstruct the three-dimensional kinematics of the knee from DMRI, thus allowing the investigation of knee deep-flexion under physiological loads in space. To improve the accuracy of the procedure, an MR-compatible rig has been developed to guide the knee flexion of the patient. We tested the procedure on three volunteers. The overall rotational and positional accuracy achieved are 1.8° ± 1.4 and 1.2 mm ± 0.8, respectively, and they are sufficient for the characterization of the joint behavior under load. Full article

Introduction: The influence of the MPFL graft in cases of patella instability with dysplastic trochlea is a controversial topic. The effect of the MPFL reconstruction as single therapy is under investigation, especially with severely dysplastic trochlea (Dejour types C and D). The purpose of this study was to evaluate the impact of trochlear dysplasia on patellar kinematics in patients suffering from low flexion patellar instability under weight-bearing conditions after isolated MPFL reconstruction. Material and Methods: Thirteen patients were included in this study, among them were eight patients with mild dysplasia (Dejour type A and B) and five patients with severe dysplasia (Dejour type C and D). By performing a knee MRI with in situ loading, patella kinematics and the patellofemoral cartilage contact area could be measured under the activation of the quadriceps musculature in knee flexion angles of 0°, 15° and 30°. To mitigate MRI motion artefacts, prospective motion correction based on optical tracking was applied. Bone and cartilage segmentation were performed semi-automatically for further data analysis. Cartilage contact area (CCA) and patella tilt were the main outcome measures for this study. Pre- and post-surgery measures were compared for each group. Results: Data visualized a trending lower patella tilt after MPFL graft installation in both groups and flexion angles of the knee. There were no significant changes in patella tilt at 0° (unloaded pre-surgery: 22.6 ± 15.2; post-surgery: 17.7 ± 14.3; p = 0.110) and unloaded 15° flexion (pre-surgery: 18.9 ± 12.7; post-surgery: 12.2 ± 13.0; p = 0.052) of the knee in patients with mild dysplasia, whereas in patients with severe dysplasia of the trochlea the results happened not to be significant in the same angles with loading of 5 kg (0° flexion pre-surgery: 34.4 ± 12.1; post-surgery: 31.2 ± 16.1; p = 0.5; 15° flexion pre-surgery: 33.3 ± 6.1; post-surgery: 23.4 ± 8.6; p = 0.068). CCA increased in every flexion angle and group, but significant increase was seen only between 0°–15° (unloaded and loaded) in mild dysplasia of the trochlea, where significant increase in Dejour type C and D group was seen with unloaded full extension of the knee (0° flexion) and 30° flexion (unloaded and loaded). Conclusion: This study proves a significant effect of the MPFL graft to cartilage contact area, as well as an improvement of the patella tilt in patients with mild dysplasia of the trochlea. Thus, the MPFL can be used as a single treatment for patient with Dejour type A and B dysplasia. However, in patients with severe dysplasia the MPFL graft alone does not significantly increase CCA. Full article

Gold nanoparticles (GNPs) have immense potential in biomedicine, but understanding their interactions with serum proteins is crucial as it could change their biological profile due to the formation of a protein corona, which could then affect their ultimate biodistribution in the body. Grafting GNPs with polyethylene glycol (PEG) is a widely used practice in research in order to decrease opsonization of the particles by serum proteins and to decrease particle uptake by the mononuclear phagocyte system. We investigated the impact of PEGylation on the formation of protein coronae and the subsequent uptake by macrophages and MDA-MB-231 cancer cells. Furthermore, we investigated the in vivo biodistribution in xenograft tumor-bearing mice using a library of 4 and 10 nm GNPs conjugated with a gadolinium chelate as MRI contrast agent, cancer-targeting aptamer AS1411 (or CRO control oligonucleotide), and with or without PEG molecules of different molecular weight (Mw: 1, 2, and 5 kDa). In vitro results showed that PEG failed to decrease the adsorption of proteins; moreover, the cellular uptake by macrophage cells was contingent on the different configurations of the aptamers and the length of the PEG chain. In vivo biodistribution studies showed that PEG increased the uptake by tumor cells for some GNPs, albeit it did not decrease the uptake of GNPs by macrophage-rich organs. Full article

Osteochondral lesion (OCL) of the patellofemoral (PF) joint is not an uncommon cause of knee pain, and surgery is needed when conservative treatment fails. However, there is a lack of evidence regarding the optimal surgical treatment for OCL of the PF joint. Fixation of OCLs using autogenous osteochondral grafts has been reported to be effective for OCL of the knee. However, in this surgical technique, the biomechanical strength of osteochondral grafts may not be sufficient in patients with open physes due to the specific quality of the cartilage and subchondral bone given their age. There is a lack of studies reporting fixation of the OCL located in the PF joint using autogenous osteochondral grafts. We herein report a case of OCL of the femoral intercondylar groove where autogenous osteochondral grafts augmented with bioabsorbable pins were used to fix the lesion in a 14-year-old patient with open physes. Preoperative MRI revealed a completely detached OCL of the intercondylar groove (36 mm × 20 mm). Although a total of four osteochondral grafts were harvested from the non-weightbearing area of the lateral femoral condyle, cartilage detached from one of the grafts. The quality of the osteochondral grafts was considered to be insufficient for stabilization of the OCL; thus, two bioabsorbable pins were additionally inserted following fixation of the lesion using three osteochondral grafts. After two years of follow-up, postoperative functional scores were favorable without knee pain. The present case suggests that fixation of the OCL using autogenous osteochondral grafts may not be appropriate for young patients with open physes. Full article

The tumor microenvironment acidification confers treatment resistance; therefore, the interference with pH regulating systems is considered a new therapeutic strategy. In this study, two human prostate cancer cell lines, PC3 and LNCaP, have been treated in vitro with proton pump inhibitors (PPIs), namely Lansoprazole, Esomeprazole (V-ATPases-inhibitors), Cariporide, and Amiloride (NHE1-inhibitors). The cell viability and pH were assessed at several drug concentrations either at normoxic or hypoxic conditions. Since Esomeprazole showed the highest toxicity towards the PC3 cancer cells compared to LNCaP ones, athymic nude mice bearing subcutaneous or orthotopic PC3 tumors were treated with Esomeprazole (dose: 2.5 mg/kg body weight) for a period of three weeks—and tumor growth was monitored. MRI-CEST tumor pH imaging with Iopamidol was performed upon treatment at 3 h, 1 week (in combination with FDG-PET), and after 2 weeks for evaluating acute, early, and late responses. Although acute tumor pH changes were observed in vivo, long-term studies on both PC3 prostate cancer models did not provide any significant change in tumor acidosis or tumor growth. In conclusion, this work shows that MRI-CEST tumor pH imaging is a valuable tool for assessing the in vivo treatment response to PPIs. Full article