Image-Guided Minimally Invasive Treatment Options for Degenerative Lumbar Spine Disease: A Practical Overview of Current Possibilities.

Lumbar back pain is one of the main causes of disability around the world. Most patients will complain of back pain at least once in their lifetime. The degenerative spine is considered the main cause and is extremely common in the elderly population. Consequently, treatment-related costs are a major burden to the healthcare system in developed and undeveloped countries. After the failure of conservative treatments or to avoid daily chronic drug intake, invasive treatments should be suggested. In a world where many patients reject surgery and prefer minimally invasive procedures, interventional radiology is pivotal in pain management and could represent a bridge between medical therapy and surgical treatment. We herein report the different image-guided procedures that can be used to manage degenerative spine-related low back pain. Particularly, we will focus on indications, different techniques, and treatment outcomes reported in the literature. This literature review focuses on the different minimally invasive percutaneous treatments currently available, underlining the central role of radiologists having the capability to use high-end imaging technology for diagnosis and subsequent treatment, allowing a global approach, reducing unnecessary surgeries and prolonged pain-reliever drug intake with their consequent related complications, improving patients' quality of life, and reducing the economic burden.

Transpedicular Contrast-enhanced CT-guided biopsy of the body and dens of the axis avoiding the trans-oral approach: Technical report and literature review.

This technical report illustrates the technique to perform computed tomography (CT)-guided bone biopsies in the body and dens of the axis (C2 vertebra) through a posterior transpedicular approach with the use of preoperative contrast-enhanced scans to highlight the course of the vertebral artery. The technique is presented through two exemplification cases: a pediatric patient with osteoblastoma and secondary aneurysmal bone cyst and one adult patient with melanoma metastasis. This case highlights the potential of the CT-guided posterolateral/transpedicular approach for performing safe and effective biopsies in the body and dens of C2, even in pediatric patients.

Osteopontin characterizes bile duct-associated macrophages and correlates with liver fibrosis severity in primary sclerosing cholangitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which pharmacological treatment options are currently unavailable. PSC is strongly associated with colitis and a disruption of the gut-liver axis, and macrophages are involved in the pathogenesis of PSC. However, how gut-liver interactions and specific macrophage populations contribute to PSC is incompletely understood. APPROACH AND RESULTS: We investigated the impact of cholestasis and colitis on the hepatic and colonic microenvironment, and performed an in-depth characterization of hepatic macrophage dynamics and function in models of concomitant cholangitis and colitis. Cholestasis-induced fibrosis was characterized by depletion of resident KCs, and enrichment of monocytes and monocyte-derived macrophages (MoMFs) in the liver. These MoMFs highly express triggering-receptor-expressed-on-myeloid-cells-2 ( Trem2 ) and osteopontin ( Spp1 ), markers assigned to hepatic bile duct-associated macrophages, and were enriched around the portal triad, which was confirmed in human PSC. Colitis induced monocyte/macrophage infiltration in the gut and liver, and enhanced cholestasis-induced MoMF- Trem2 and Spp1 upregulation, yet did not exacerbate liver fibrosis. Bone marrow chimeras showed that knockout of Spp1 in infiltrated MoMFs exacerbates inflammation in vivo and in vitro , while monoclonal antibody-mediated neutralization of SPP1 conferred protection in experimental PSC. In human PSC patients, serum osteopontin levels are elevated compared to control, and significantly increased in advanced stage PSC and might serve as a prognostic biomarker for liver transplant-free survival. CONCLUSIONS: Our data shed light on gut-liver axis perturbations and macrophage dynamics and function in PSC and highlight SPP1/OPN as a prognostic marker and future therapeutic target in PSC.

Limitations of PLX3397 as a microglial investigational tool: peripheral and off-target effects dictate the response to inflammation.

Microglia, the resident macrophages of the central nervous system (CNS), play a critical role in CNS homeostasis and neuroinflammation. Pexidartinib (PLX3397), a colony-stimulating factor 1 (CSF1) receptor inhibitor, is widely used to deplete microglia, offering flexible options for both long-term depletion and highly versatile depletion-repopulation cycles. However, the potential impact of PLX3397 on peripheral (immune) cells remains controversial. Until now, the microglia-specificity of this type of compounds has not been thoroughly evaluated, particularly in the context of peripherally derived neuroinflammation. Our study addresses this gap by examining the effects of PLX3397 on immune cells in the brain, liver, circulation and bone marrow, both in homeostasis and systemic inflammation models. Intriguingly, we demonstrate that PLX3397 treatment not only influences the levels of tissue-resident macrophages, but also affects circulating and bone marrow immune cells beyond the mononuclear phagocyte system (MPS). These alterations in peripheral immune cells disrupt the response to systemic inflammation, consequently impacting the phenotype irrespective of microglial depletion. Furthermore, we observed that a lower dose of PLX3397, which does not deplete microglia, demonstrates similar (non-)MPS effects, both in the periphery and the brain, but fails to fully replicate the peripheral alterations seen in the higher doses, questioning lower doses as a 'peripheral control' strategy. Overall, our data highlight the need for caution when interpreting studies employing this compound, as it may not be suitable for specific investigation of microglial function in the presence of systemic inflammation.

Percutaneous CT-Guided Bone Biopsies: Indications, Feasibility and Diagnostic Yield in the Different Skeletal Sites-From the Skull to the Toe.

CT-guided bone biopsies are currently the diagnostic tool of choice for histopathological (and microbiological) diagnoses of skeletal lesions. Several research works have well-demonstrated their safety and feasibility in almost all skeletal regions. This comprehensive review article aims at summarizing the general concepts in regard to bone biopsy procedures, current clinical indications, the feasibility and the diagnostic yield in different skeletal sites, particularly in the most delicate and difficult-to-reach ones. The choice of the correct imaging guidance and factors affecting the diagnostic rate, as well as possible complications, will also be discussed. Since the diagnostic yield, technical difficulties, and complications risk of a CT-guided bone biopsy significantly vary depending on the different skeletal sites, subdivided analyses of different anatomical sites are provided. The information included in the current review article may be useful for clinicians assisting patients with possible bone neoplasms, as well as radiologists involved in the imaging diagnoses of skeletal lesions and/or in performing bone biopsies.

The New Ice Age of Musculoskeletal Intervention: Role of Percutaneous Cryoablation in Bone and Soft Tissue Tumors.

In the rapidly evolving field of interventional oncology, minimally invasive methods, including CT-guided cryoablation, play an increasingly important role in tumor treatment, notably in bone and soft tissue cancers. Cryoablation works using compressed gas-filled probes to freeze tumor cells to temperatures below -20 °C, exploiting the Joule-Thompson effect. This cooling causes cell destruction by forming intracellular ice crystals and disrupting blood flow through endothelial cell damage, leading to local ischemia and devascularization. Coupling this with CT technology enables precise tumor targeting, preserving healthy surrounding tissues and decreasing postoperative complications. This review reports the most important literature on CT-guided cryoablation's application in musculoskeletal oncology, including sarcoma, bone metastases, and bone and soft tissue benign primary tumors, reporting on the success rate, recurrence rate, complications, and technical aspects to maximize success for cryoablation in the musculoskeletal system.

Ultrasound-Guided Percutaneous Bone Biopsy: Feasibility, Diagnostic Yield and Technical Notes.

While nowadays, CT-guided bone biopsy represents the gold standard tool for histopathological and microbiological diagnosis of skeletal lesions, the role of US-guided bone biopsy has not yet been fully explored. US-guided biopsy offers several advantages, such as the absence of ionizing radiation, fast acquisition time, as well as good intra-lesional echo, and structural and vascular characterization. Despite that, a consensus in regard to its applications in bone neoplasms has not been established. Indeed CT-guided technique (or fluoroscopic ones) still represents the standard choice in clinical practice. This review article aims to review the literature data about US-guided bone biopsy, underlying clinical-radiological indications, advantages of the procedure and future perspectives. Bone lesions taking the best advantages of the US-guided biopsy are osteolytic, determining the erosion of the overlying bone cortex and/or with an extraosseous soft-tissue component. Indeed, osteolytic lesions with extra-skeletal soft-tissue involvement represent a clear indication for US-guided biopsy. Moreover, even lytic bone lesions with cortical thinning and/or cortical disruption, especially located in the extremities or pelvis, can be safely sampled with US guidance with very good diagnostic yield. US-guided bone biopsy is proven to be fast, effective and safe. Additionally, it offers real-time needle evaluation, an advantage when compared to CT-guided bone biopsy. In the current clinical settings, it seems relevant to select the exact eligibility criteria for this imaging guidance since the effectiveness can vary depending on the type of lesion and body site involved.

Kupffer Cells Contested as Early Drivers in the Pathogenesis of Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is an idiopathic chronic immune-mediated cholestatic liver disease characterized by fibro-inflammatory bile duct strictures, progressive hepatobiliary fibrosis, and gut-liver axis disruption. The pathophysiology of PSC remains insufficiently characterized, which hampers the development of effective therapies. Hepatic macrophages (MFs) such as Kupffer cells (KCs) are implicated in PSC pathogenesis, but their exact role is unclear. Using the latest markers to discriminate resident KCs (ResKCs) from their monocyte-derived counterparts (MoKCs), and two models of intrahepatic and extrahepatic cholestasis, respectively, this study showed that CLEC4F+TIM4+ ResKCs were depleted after chronic cholestatic liver injury. The infiltrating CLEC4F+TIM4- MoKCs were already enriched during the acute phase of PSC. Transcriptional profiling of hepatic MF subsets during early cholestatic injury indicated that ResKCs were indeed activated and that MoKCs expressed higher levels of pro-inflammatory and proliferative markers compared with those of ResKCs. As indicated in experiments with Clec4fDTR transgenic mice, conditional depletion of KCs, before and during early cholestasis induction, had no effect on the composition of the hepatic myeloid cell pool following injury progression and did not affect disease outcomes. Taken together, these results provide new insights into the heterogeneity of the MF pool during experimental PSC and evidence that depletion of resident and activated KCs during sclerosing cholangitis does not affect disease outcome in mice.

Could Spinal Epidural Lipomatosis Be the Hallmark of Metabolic Syndrome on the Spine? A Literature Review with Emphasis on Etiology.

Spinal epidural lipomatosis is defined by an excessive amount of epidural fat in the spinal canal, usually in the lumbosacral tract: a well-known cause of lumbar pain and spinal stenosis with a possible wide range of neurological symptoms. Recent research data reveal that, nowadays, obesity has become the main cause of spinal epidural lipomatosis. Moreover, this condition was recently recognized as a previously unknown manifestation of metabolic syndrome. Radiological studies (CT and MRI) are the only tools that are able to diagnose the disease non-invasively. Indeed, radiologists play a key role in disease recognition, with subsequent possible implications on patients' systemic health assessments. Despite its clinical importance, the condition is still underreported and neglected. The current literature review summarizes all the main etiologies of spinal epidural lipomatosis, particularly regarding its linkage with metabolic syndrome. An overview of disease characteristics from diagnosis to treatment strategies is also provided.

CT-Guided Radiofrequency Thermal Ablation for the Treatment of Atypical, Early-Onset Osteoid Osteoma in Children Younger than 4 Years Old: Single-Institution Experience and Literature Review.

The aim of our study is to report our experience on CT-guided radiofrequency ablation (RFA) for osteoid osteoma (OO) in children under 4 years of age and to review the literature regarding this atypical, early onset of the disease. We retrospectively reviewed the clinical and radiological records of the patients treated with CT-guided RFA for OO at our institution (2006−2021), including those under 4 years of age. Data regarding technical success, clinical success, and biopsy diagnostic yield were collected. Moreover, we performed a literature review including previous articles on early-onset OO. We found only 12 patients that were under 4 years of age (12/842−1.4%) at the time of RFA treatment: 4 F and 8 M, mean age at the time of the treatment 35.3 months (range 22−46 months). The mean follow-up was 22.8 months (range 6−96 months). Technical success was achieved in all cases (12/12). In all patients (12/12), a complete remission of the pain symptoms was achieved at clinical follow-up controls. No recurrence of pain or complications were documented. The histopathological diagnosis was confirmed in 4 patients (4/12−33.3%). Moreover, we found another 9 articles in the literature with a main focus on early-onset OO (<4 years old), with a total of 12 patients included; 6 of those patients (6/12−50%) were treated with CT-guided RFA, with success reported 5 cases (5/6−83.3%). Our series of cases treated at a single institution, together with the existing data from the literature, confirms that CT-guided RFA is effective and safe for the treatment of osteoid osteoma, even in atypical, early onset in children under 4 years of age.

Reduction of Metal Artifacts Caused by Titanium Peduncular Screws in the Spine by Means of Monoenergetic Images and the Metal Artifact Reduction Software in Dual-Energy Computed Tomography.

Objectives: To evaluate the reduction of metal artifacts in patients with titanium peduncular screws in the spine using (1) conventional images (CI), (2) virtual monoenergetic reconstructions (VMRs), and (3) VMR + Metal Artifact Reduction Software (VMR + MARS), with dual-energy computed tomography (DECT). Materials and Methods: Twenty-four patients with titanium peduncular screws in the spine were studied using a 64-channel DECT. During the postprocessing phase, the CI, the VMRs from 100 to 140 keV, and the VMR at 140 keV + MARS were synthesized. All the images were considered, and a quantitative evaluation was performed measuring the attenuation values (in terms of Hounsfield Units) with region of interest, in correspondence with the most hyperdense and hypodense artifacts. All the values were then compared. A qualitative evaluation, in terms of image quality and extent of artifacts, was also performed by two radiologists. Results: In quantitative terms, the 140 keV + MARS reconstruction was able to significantly reduce both bright and dark metal artifacts, compared to CI and to VMRs. The VMR was capable of significantly reducing both dark and bright artifacts, compared to CI. In qualitative terms, the VMR at 140 keV proved to be the best, compared to CI and VMR + MARS images. Conclusions: The VMR + MARS image reduces metal artifacts from titanium peduncular screws more than VMRs alone and CI. Furthermore, the VMR can decrease metal artifacts from a quantitative and a qualitative point of view. Combining information from VMRs and VMR + MARS images could be the best way to solve the issue of metal artifacts on computed tomography images.

Modulating hepatic macrophages with annexin A1 in non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) and associated end-stage liver disease is a growing cause of concern throughout the Western world. It constitutes a significant clinical burden for which therapeutic approaches are very limited. Over the last years, considerable attention has therefore been paid to identifying potential therapeutic strategies to reduce this burden. Annexin A1 (AnxA1), a calcium-phospholipid binding protein, has been proposed to be a negative regulator of inflammation in the context of NASH. In a recent publication, Gadipudi, Ramavath, Provera et al. investigated the therapeutic potential of Annexin A1 treatment in preventing the progression of NASH. They demonstrate that treatment of mice with NASH with recombinant human AnxA1 can reduce inflammation and fibrosis without affecting steatosis or metabolic syndrome. This was proposed to be achieved through the modulation of the macrophage populations present in the liver. Here, we discuss the main findings of this work and raise some outstanding questions regarding the possible mechanisms involved and the functions of distinct macrophage populations in NASH.

Ultrasound-guided percutaneous irrigation of calcific tendinopathy outside the rotator cuff: short-term evaluation.

RATIONALE AND OBJECTIVES: While ultrasound-guided percutaneous irrigation for painful calcific tendinopathy (US-PICT) is the treatment of choice for the rotator cuff, there is a lack of knowledge regarding the treatment of this condition with atypical location. The purpose of our study is to assess if US-PICT can be applied safely and successfully in atypical sites, outside of the rotator cuff. MATERIALS AND METHODS: We retrospectively reviewed the US-PICT performed outside the rotator cuff, in the last 5 years in a single institution. A total of 16 patients have been included in this study. We collected the values of the numerical rating scale (NRS) for pain pre- and post-procedure (7 days and 3-month follow-up). Moreover, we assessed the imaging studies available pre- and post-procedure (ultrasound and plain radiography) to assess complications. RESULTS: In all the 16 patients (10F, 6 M; mean age 50.2; range 24-65-year-old), no complications have been observed during and after the procedures. The mean pain NRS before treatment was 8.7 (range 10-6) and dropped to 1.1 (6-0) after 1 week as well after 3 months 1.1 (6-0). The NRS pain reduction from baseline resulted to be statistically significant after 7 days and 3 months (p < 0.001). CONCLUSION: Our results suggest the safety and efficacy of this procedure, underlining the great potential of US-PICT applied even in different atypical locations.

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.

Underreporting of spinal epidural lipomatosis: A retrospective analysis of lumbosacral MRI examinations from different radiological settings.

PURPOSE: The purpose of this study was to assess the rate with which radiologists reported spinal epidural lipomatosis (SEL) when interpreting lumbosacral magnetic resonance imaging (MRI) examination. MATERIALS AND METHODS: A total of 450 lumbosacral MRI examinations obtained in 450 patients were included (199 men, 251 women; mean age, 56.7 ± 13.5 [SD] years; age range: 18-91 years).  Three senior radiologists assessed and classified independently SEL on MRI according to the Borré grading system (Grade 1 to Grade 3). Depiction of SEL on MRI reports (i. e., reporting rate) and association with patients' symptoms were verified. RESULTS: SEL was found in 75/450 patients (prevalence = 16.7%), and classified as grade-1 (mild) in 49/75 (65.3%) patients, grade-2 (moderate) in 24/75 (32%), and grade-3 (severe) in 2/75 (2.7%). SEL was diagnosed on MRI report in 6/75 (8%) patients. SEL prevalence based on MRI reports was 1.3% (6/450), significantly lower than its actual prevalence based on MRI examinations (P < 0.0001). The reporting rate was 0% in grade-1 (0/19), 10.2% in grade-2 (5/49) and 50.0% in grade-3 (1/2), and variable on the radiologist subspecialty (10.0% among musculoskeletal radiologists, 11.1% among neuroradiologists, and 3.7% among generalists). SEL was considered as the only cause of symptoms in 7/75 patients (9.3%) and a concurrent cause in 9/75 (12%). CONCLUSION: SEL reporting rate is extremely low, leading to an important underestimation of disease prevalence. SEL diagnosis and grading should be refined to improve reports quality and subsequently patient care.

Ultrasound-guided Treatments for the Painful Shoulder.

Shoulder pain is an extremely common condition. The painful shoulder may be the result of a wide spectrum of underlying pathological conditions, including calcific tendinopathy of the rotator cuff, subacromial-subdeltoid bursitis, acromioclavicular or glenohumeral arthritis, tenosynovitis of the long biceps tendon, rotator cuff lesions, and many other less common conditions. Ultrasound imaging is an effective tool for the diagnosis and also for the image guidance of treatment of the majority of these conditions. Several ultrasound-guided procedures are effective for pain relief, such as percutaneous irrigation, intra-bursal or intra-articular drugs injection, fluid aspiration, neural block. This review article aims to summarize and discuss the most common treatment possibilities with ultrasound guidance for the painful shoulder.

Imaging of calcific tendinopathy in atypical sites by ultrasound and conventional radiography: A pictorial essay.

Calcific tendinopathy (CT) is a very common condition caused by the deposition of calcium hydroxyapatite crystals in tendons and it can be an incidental finding or associated with severe pain. CT can be easily detected by first level exams such as traditional radiography and ultrasound (US), which provide information on the site, extent and composition of the calcific formation. Classically, the most affected site is represented by the rotator cuff tendons, in particular the supraspinatus tendon. In this pictorial essay we illustrate various unusual localizations of CT detected by US and plain radiography, in order to provide an overview with the aim of preventing diagnostic delays and consequently CT complications.

Soft Tissue Sarcomas: The Role of Quantitative MRI in Treatment Response Evaluation.

BACKGROUND: Although curative surgery remains the cornerstone of the therapeutic strategy in patients with soft tissue sarcomas (STS), neoadjuvant radiotherapy and chemotherapy (NART and NACT, respectively) are increasingly used to improve operability, surgical margins and patient outcome. The best imaging modality for locoregional assessment of STS is MRI but these tumors are mostly evaluated in a qualitative manner. OBJECTIVE: After an overview of the current standard of care regarding treatment for patients with locally advanced STS, this review aims to summarize the principles and limitations of (i) the current methods used to evaluate response to neoadjuvant treatment in clinical practice and clinical trials in STS (RECIST 1.1 and modified Choi criteria), (ii) quantitative MRI sequences (i.e., diffusion weighted imaging and dynamic contrast enhanced MRI), and (iii) texture analyses and (delta-) radiomics.

MRI in differential diagnosis between tuberculous and pyogenic spondylodiscitis.

PURPOSE: The aim of the study was to investigate whether MRI findings together with epidemiological data could help in differentiating between tuberculous and pyogenic spondylodiscitis. METHODS: Clinical records of 260 patients with a suspicion of spondylodiscitis were analysed. Patients were selected using the following inclusion criteria: confirmed diagnosis of spondylodiscitis either from pyogenic bacteria or from Mycobacterium tuberculosis and contrast-enhanced MRI performed before treatment. Clinical data concerning age, sex and country-of-origin were also collected. For each patient, several MRI-features were evaluated by two-expert musculoskeletal radiologists. A chi-squared test and a multiple logistic regression were used to find the best predictors of tuberculous or pyogenic spondylodiscitis. RESULTS: 114 patients were retrospectively enrolled, 30 with tuberculous and 84 with pyogenic spondylodiscitis. We found 18 MRI-features, significantly different between the two groups. Among these, the most strongly associated with tuberculous spondylodiscitis were: heterogeneous vertebral signal on T1w-sequences (Odds Ratio(OR) = 205.759-p < 0.001), presence of epidural abscess (OR = 86.221-p < 0.001), severe vertebral destruction (OR = 10.017-p < 0.001) and absence of epidural phlegmon (OR = 86.221-p < 0.001). Moreover, patients coming from countries with a middle-high prevalence of tuberculosis were more frequently affected by tuberculous spondylodiscitis than others were (OR = 229.136-p < 0.001). The best prediction model demonstrated a correct classification rate of 94.7%. CONCLUSION: To the best of our knowledge this is the largest study comparing MRI-features of tuberculous and pyogenic spondylodiscitis. The above-mentioned MRI-features and epidemiological data are crucial in the differential diagnosis between these two entities, guiding the choice of the appropriate therapy, especially when a pathogen cannot be clearly identified with other modalities.