[ 18 F]FDG Positron Emission Tomography for Initial Staging and Healing Assessment at the End of Therapy in Lymph Nodes and Bone Tuberculosis.

Objective: In extra-pulmonary tuberculosis, therapeutic management is difficult in the absence of reliable tool to affirm healing at the end of treatment. In this prospective multicenter study, we evaluated [18F]FDG-PET for this purpose. Methods: Forty-two patients out of 55 included patients could be analyzed. Additionally to usual biological, histological and morphological explorations, [18F]FDG-PET was performed at diagnosis (PET1), at the end of treatment (PET2), indeed 6 months later. Then patients were followed until 12 months after end of prescribed treatment. Results: PET1 was positive in 97.6% of patients and discovered unknown injured sites in 52.7% of cases. PET2 was positive in 83.3% of uncured patients, and in 82.3% of cured patients. The sum and mean value of SUVmax measured in PET/CT lesions decreased between PET1 and PET2 in all patients. Mean value of SUVmax (MSUV) and sum value of SUVmax on PET2 showed the highest AUC on ROC curves for the diagnosis of healing at the end of prescribed treatment; MSUV 3.5 on PET2 had a sensitivity of 76.5% and a specificity of 80.0% to affirm healing at the end of prescribed treatment. Conclusions: [18F]FDG-PET/CT was useful at diagnosis, discovering unknown lesions in 52.7% of cases. MSUV on PET2 was the best criteria to affirm healing at the end of prescribed treatment.

Bone metastasis: mechanisms, therapies, and biomarkers.

Skeletal metastases are frequent complications of many cancers, causing bone complications (fractures, bone pain, disability) that negatively affect the patient's quality of life. Here, we first discuss the burden of skeletal complications in cancer bone metastasis. We then describe the pathophysiology of bone metastasis. Bone metastasis is a multistage process: long before the development of clinically detectable metastases, circulating tumor cells settle and enter a dormant state in normal vascular and endosteal niches present in the bone marrow, which provide immediate attachment and shelter, and only become active years later as they proliferate and alter the functions of bone-resorbing (osteoclasts) and bone-forming (osteoblasts) cells, promoting skeletal destruction. The molecular mechanisms involved in mediating each of these steps are described, and we also explain how tumor cells interact with a myriad of interconnected cell populations in the bone marrow, including a rich vascular network, immune cells, adipocytes, and nerves. We discuss metabolic programs that tumor cells could engage with to specifically grow in bone. We also describe the progress and future directions of existing bone-targeted agents and report emerging therapies that have arisen from recent advances in our understanding of the pathophysiology of bone metastases. Finally, we discuss the value of bone turnover biomarkers in detection and monitoring of progression and therapeutic effects in patients with bone metastasis.

Osteoblastic and hyperostotic craniofacial lesion detected by 99mTc-labeled methylene diphosphonate bone scintigraphy and single-photon emission computed tomography/computed tomography: a pictorial essay.

99mTc-bisphophonates bone scan, planar and single-photon emission computed tomography/computed tomography (SPECT/CT) modalities, is a commonly used technique that provides high sensitivity and specificity for detection of osseous metastases. However, besides bone metastases, SPECT/CT provides an accurate evaluation of the localization of the lesions and supplies anatomic information that can be valuable for diagnosis of nonmalignant bone diseases, occasionally disclosed in the skull. Reporting of craniofacial lesions detected by 99mTc-MDP (99mTc-labeled methylene diphosphonate) bone scintigraphy and SPECT/CT in the literature is limited. The aim of this pictorial review is to present the findings detected by 99mTc-MDP bone scintigraphy and SPECT/CT including cases under two broad categories: osteoblastic and hyperostosis craniofacial lesions.

Adapting palliative radiation therapy for bone metastases during the Covid-19 pandemic: GEMO position paper.

The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases.

Bloodpool SPECT as part of bone SPECT/CT in painful total knee arthroplasty (TKA): validation and potential biomarker of prosthesis biomechanics.

PURPOSE: To compare bloodpool SPECT with planar imaging in bone SPECT/CT of painful total knee arthroplasty (TKA) with respect to inter-rater agreement, confidence, prosthesis outcome, and biomechanical functioning. METHODS: Retrospective study of bloodpool SPECT and planar control images. Four raters used the validated Bruderholz scheme and a 5-point scale to grade uptake. Inter-rater agreement and overall confidence scores were calculated. Variable cluster analysis was performed to identify patterns of uptake, and associations between patterns and prosthesis outcome and biomechanical functioning were examined. RESULTS: In all, 55 knees in 43 patients were analyzed (median follow-up 17 months; revision rate 21.8%). SPECT significantly improved inter-rater agreement in 24% of regions (all P < 0.05) and overall confidence by 20% (P < 0.001). Regional uptake cluster analysis showed improved antero-posterior separation with SPECT, and distinct patterns associated with prosthesis survival in lateral femoral (P = 0.041) and medial tibial (P < 0.001) regions. The prognostic value of SPECT outperformed planar imaging for tibial (P < 0.001), patellar (P = 0.009), and synovial (P = 0.040) assessment. Internal femoral malrotation resulted in increased uptake in posteromedial (P = 0.042) and anterolateral (P = 0.016) femoral, and lateral patellar (P = 0.011) regions. Internal tibial malrotation increased uptake in posterolateral (P = 0.026) and posteromedial tibial (P = 0.005), and medial patellar regions (P = 0.004). Bloodpool SPECT improved the prognostic value of late-phase SPECT/CT for the assessment of the medial tibial region. CONCLUSIONS: Bloodpool SPECT outperforms planar assessment of painful TKAs and the identification of distinct uptake patterns make it a potentially clinically relevant biomarker of prosthesis survival and biomechanical functioning.

Bone SPECT/CT in Postoperative Spine.

Back pain is a common problem and the diagnosis and treatment depend on the clinical presentation, yet overlap between pain syndromes is common. Imaging of patients with chronic back pain in both pre- and postoperative scenarios include radiological, radionuclide, and hybrid techniques. In general, these techniques have their own advantages and limitations. The aim of surgery is to eliminate pathologic segmental motion and accompanying symptoms, especially pain. However, surgical procedures are not without complications and localizing the cause of the pain is often challenging. Radiobisphosphonate bone SPECT/CT is reported to be useful in evaluating benign orthopedic conditions and it often provides valuable information such as accurate localization and characterization of bone abnormalities. In this review, routinely used spinal surgical techniques and procedures are discussed, as well as the acute and delayed complications related to spinal surgery, the role of conventional imaging, and the potential uses of radionuclide bone SPECT/CT to diagnose pseudoarthrosis, cage subsidence, loosening and misalignment, hardware failure, and postoperative infection.

SPECT/CT in Postoperative Hand and Wrist Pain.

In this review we summarize the current evidence and experience regarding the performance of SPECT/CT in the evaluation of patients with postoperative painful wrist or hand. There is a wide range of operative wrist and hand interventions due to congenital, traumatic, degenerative, or inflammatory diseases. A significant number of patients suffer from pain after operative procedures. Several imaging modalities have been used to evaluate the reason for painful postoperative wrists like standard conventional x-rays, ultrasound, CT, MRI, or bone scintigraphy. In the last decade, bone SPECT/CT has offered a new approach in combining metabolic and morphologic cross-sectional information in patients with painful postoperative wrists and is increasingly used if standard imaging fails to identify the pain generator. SPECT/CT is less hampered by artifacts caused by metallic implants and shows more details of the cortical bone compared with MRI. MRI is generally superior regarding visualization of soft tissue structures like tendons, synovia, cartilage, muscles, and ligaments. SPECT/CT arthrography has been established to enable the assessment of cartilage and ligament tears.

SPECT/CT in Postoperative Painful Hip Arthroplasty.

Consecutive milestones in hip arthroplasty design and surgical technique have contributed to the successful and cost-effective intervention this procedure has become today in maintaining mobility and quality of life in patients with osteoarthritis, fracture, or other hip conditions. With the increasing prevalence of hip joint replacements, the need for improved diagnostic imaging tools to guide revision surgery has risen in parallel. Over the last few years, promising data have emerged on the potential role of bone SPECT/CT imaging in the assessment of patients with recurrent pain after arthroplasty. This review summarizes the trends in hip arthroplasty surgery (partial vs total arthroplasty; cemented vs cementless arthroplasty; resurfacing arthroplasty) and prosthesis design (bearing materials; stem designs) over the last decade. In particular, the impact on the biomechanics and interpretation of bone SPECT/CT findings is discussed, with emphasis on integrative reporting in the following frequently encountered conditions: lysis/aseptic loosening, septic loosening, heterotopic ossification, periprosthetic fracture, tendinopathies, and adverse local tissue reactions. Based on the available literature data, bone SPECT/CT is increasingly being used as second-line imaging modality when conventional investigations are nondiagnostic. Further outcome research is warranted to examine whether this technique could be used earlier in patient management.

SPECT/CT in Postoperative Foot and Ankle Pain.

Postoperative pain is a clinically relevant issue in orthopedic patients, affecting more than 40% 1 year after foot and ankle surgery. Because of the very complex anatomy with many different joints and several motion axes, clinical examination and conventional imaging are sometimes not sufficient to identify a local pain generator. Local uptake of bone-seeking radiopharmaceuticals is known to correlate accurately with sites of pain generating foci and, thus, bone scintigraphy has been an established method to evaluate these respective patients for many years. However, the specificity is rather low if only planar images are acquired. The development of SPECT and especially of hybrid SPECT and CT imaging has significantly enhanced the specificity of this technique. The combination of both functional and morphological imaging, ideally performed with a dedicated SPECT/CT system to minimize misregistration owing to motion artifacts and to enhance image quality by attenuation correction, allows an early and reliable detection of pathologic bone processes, even in patients where radiological imaging with MRI or CT is hampered by metal implants. In diabetic patients with a neuropathic Charcot osteoarthropathy, infection can be differentiated from inflammatory bone alterations (causing bone marrow edema) almost certainly using SPECT/CT with radiolabeled white blood cells and antigranulocyte antibodies, allowing an individual and precise treatment planning either in the initial course of the disease or even after surgery. This article reviews the most frequent clinical challenges in patients after foot and ankle surgery, including a description of the various surgical procedures, the different imaging options with their advantages and disadvantages, and aims to integrate bone SPECT/CT into the clinical diagnostic workup.

SPECT/CT in the Postoperative Painful Knee.

This review summarizes the role of SPECT/CT in patients with a painful postoperative knee and describes typical diagnostic criteria in these patients. Pain after knee surgery is common and is influenced by the underlying pathology, the type of surgery, and the patient. Knee joint-preserving surgery includes osteotomy, ligament reconstruction, meniscus surgery, and cartilage repair procedures, often used in combination. Knee arthroplasty procedures consist of unicondylar, patellofemoral, and primary or revision total knee prosthesis. In patients with pain after knee joint-preserving surgery, MRI remains the reference standard. After ligament reconstruction, CT can evaluate postoperative tunnel positioning, and bone SPECT/CT can contribute by assessing overloading or biodegradation problems. After meniscal or cartilage surgery, SPECT/CT can be particularly helpful to identify compartment overloading or nonhealing chondral or osteochondral lesions as cause of pain. SPECT/CT arthrography can assess cartilage damage at an early stage due to altered biomechanical forces. After corrective osteotomy of the knee, SPECT/CT can reveal complications such as overloading, nonunion, or patellofemoral problems. After arthroplasty, conventional radiographs lack both sensitivity to detect aseptic loosening and specificity in differentiating aseptic from infectious loosening. Secondly, hardware-induced artifacts still hamper CT and MRI, despite improving and increasingly available metal artifact reduction techniques. Bone scintigraphy is a proven useful adjunct to conventional radiography and MRI to reveal the pain generator and is less hampered by artifacts from metallic implants compared with CT and MRI. Nevertheless, the optimal imaging strategy in evaluating complications after knee arthroplasty is still a matter of debate. Although the evidence of the use of BS SPECT/CT is still limited, it is growing steadily. In particular, recent data on specific uptake patterns in tibial and femoral zones after total knee arthroplasty and the impact of integrating biomechanics into the assessment of SPECT/CT appear promising, but more research is needed.

Osteopenia and fractures associated with long-term therapy with MEK inhibitors.

Targeted therapies have markedly improved the survival of patients with melanoma. We report the case of two patients with advanced melanoma controlled by long-term MEK inhibitor or combination of BRAF and MEK inhibitors, who developed fractures related to severe osteopenia. A 48-year-old woman was treated by pimasertib after the failure of two lines of chemotherapy, and a 42-year-old man was treated by an association of BRAFi (dabrafenib) and MEKi (trametinib) after the failure of one line of chemotherapy. During follow-up, both complained of buttock pain, revealing primary fractures of the pelvis and lumbar vertebra. In both patients, none had osteoporosis risk factors; DEXA scan revealed osteopenia, and analysis ruled out metastatic bone lesion or secondary osteoporosis. Zoledronic acid, cholecalciferol (vitamin D3), oral calcium, and pain killers were introduced, leading to no further bone event. Numerous pathways are involved in the homeostasis of bone turnover, and the effect of tyrosine kinase inhibitors on those pathways is not well known yet. The absence of usual causes of osteoporosis or metastatic bone lesion and kinetics of symptoms lead us to suggest that MEK inhibitors were responsible for the development of osteoporosis. To the best of our knowledge, this is the first report of fractures associated with osteopenia in patients treated with MEKi. Long-term survival owing to new targeted treatment could be associated with yet underestimated adverse effects such as osteopenia/osteoporosis that could impair patient's quality of life and should be investigated.

99mTc-HMPAO-leukocyte scintigraphy for diagnosis and therapy monitoring of skull base osteomyelitis.

OBJECTIVE: Skull base osteomyelitis (SBO) is a rare but life-threatening disease observed in elderly diabetic patients, with high risk of recurrence and difficult therapeutic management. The diagnosis is ascertained from a set of clinical, biological, and imaging findings. CT and MRI allow initial diagnosis, but are not accurate to affirm healing at the end of therapy. 99mTc-HMPAO-Leucocyte Scintigraphy (LS) is highly sensitive and specific for the detection of infection. The aim of this study was to evaluate LS i) for initial diagnosis, and ii) to confirm healing at the end of antibiotherapy in SBO. STUDY DESIGN: We retrospectively reviewed from November 2011 to September 2015 all patients with confirmed SBO who underwent LS twice, at diagnosis and at the end of antibiotic therapy in our nuclear medicine department (n = 27). METHODS: Clinical, biological, CT, LS, and follow-up data were recorded in all patients. LS images (planar and tomographic performed 4 hours and 24 hours after intravenous injection of autologous Tc-99m-HMPAO-leucocytes) were visually assessed and quantified. RESULTS: At initial diagnosis, 25 of 27 patients had a positive LS. At the end of antibiotic therapy (3 ± 1 months duration), 26 of 27 patients had a negative LS. During subsequent follow-up (= or >6 months), the disease recurred in four patients including three with a negative postantibiotherapy LS scan. CONCLUSION: In this retrospective study, LS was powerful for initial diagnostic of SBO and for healing assessment at the end of antibiotic therapy. We conclude it is a useful technique for therapeutic monitoring of SBO. LEVEL OF EVIDENCE: 4.

Bone scan usefulness in patients with painful hip or knee prosthesis: 10 situations that can cause pain, other than loosening and infection.

In recent years, with the higher median life expectancy, the number of hip and knee replacements has increased. Clinical examination and morphological studies are essential to evaluate patients with a painful arthroplasty. Nuclear medicine examinations also play an important role, their main usefulness being the exclusion of prosthesis complications. Nevertheless, conventional examinations, namely bone scan and white blood cell scintigraphy, can also identify complications, such as loosening and infection. This study describes the normal and pathologic patterns of a bone scan and exemplifies ten common situations that can cause pain in patients with hip or knee arthroplasty, other than loosening and infection, which can be disclosed on a bone scintigraphy. The ten situations that should be considered and looked for when analysing a bone scan are: referred pain, patellofemoral pain syndrome, fractures, fissures, abscess/haematoma, bone insert behaviour, heterotopic ossification, greater trochanter pseudarthrosis, osteoarthritis extension in a knee with an unicompartmental prosthesis, and systemic disease with bone involvement.