Monitoring tumor metastases and osteolytic lesions with bioluminescence and micro ct imaging ed lim 1, kshitij modi 1, anna christensen 1, jeff meganck 1, stephen oldfield 1, ning zhang 1 1 imaging biology research and development, caliper life sciences. In vivo nearinfrared fluorescence imaging of osteoblastic. Effect of bone reading ct software on radiologist performance. However, this distinction is not absolute, and many patients have a mixed picture of both osteolytic and osteoblastic metastases table 1. However, bone metastases can eventually cause severe and debilitating effects and seriously impair quality of life without timely treatment. Skeletal metastases account for 70 % of all malignant bone tumors, and are seen in a vast number of primary cancers. Bone metastases are generally classified as osteolytic or osteoblastic based upon a radiologic appearance that demonstrates predominant bone destruction or deposition of new bone. Military population and proposal of a new mri classification system. Monitoring the response of bone metastases to treatment with magnetic resonance imaging and nuclear medicine techniques. At the same time, there has been an increase in the use of other hybrid techniques for imaging of the. Advances in medical imaging applied to bone metastases.
Prostate cancer produces painful osteoblastic bone metastases. Petct imaging of osteoblastic bone metastases with 68 ga. Susceptibilityweighted mri achieved a sensitivity of 100% 38 of 38 and specificity of 96% 25 of 26 for predominantly osteoblastic metastases and a sensitivity of 96% 25 of 26 and specificity of 100% 38 of 38 for predominantly osteolytic metastases. Another case again shows innumerable, rounded sclerotic lesions. Although prostate cancer cells produce numerous osteogenic factors, to date, none have been shown to mediate osteoblastic bone metastases in an in vivo model of prostate cancer. Wholebody mri has become feasible with recent developments in mri, including fast image acquisition, hardware innovation such as tabletop extenders, and the implementation of dedicated software 7. Detection of osseous metastases is crucial for accurate staging and optimal treatment planning of lymphoma. However, osseous metastases are infrequently silent. Imaging has always played a key role in the diagnosis of bone metastases in breast cancer and planar 99m tcdiphosphonate bone scanning bs remains widely used, its lack of specificity has been improved with the addition of spect and spectct. Shingo iwano and colleagues from nagoya university in japan and fujifilm plos one, january 17, 2017. In this study, after using bone reading software, the detection rate was improved in both experienced and inexperienced radiologists.
Multiple osteoblastic metastases to the pelvis and lumbar vertebral bodies from carcinoma of the prostate. Osteoblastic metastases from breast carcinoma with false. This feature accounts for the variable sensitivity and specificity of different imaging modalities. Imaging characteristic analysis of metastatic spine lesions from breast, prostate, lung, and. Imaging bone metastases from prostate cancer presents several challenges. This article will focus only on the metastasis involving the bony structures of the spine. May 20, 2016 to evaluate screening and diagnostic accuracy for the detection of osteoblastic rib lesions using an advanced postprocessing package enabling inplane rib reading in ctimages. Osteoblastic metastases mimickers on contrast enhanced ct. Aug 18, 2016 while imaging has become an integral part of diagnosing patients presenting with malignancy, it can be confusing when an osteoblastic lesion is identified in the presence and absence of a primary. Imaging tests to find bone metastases imaging tests use xrays, magnetic fields, or radioactive substances to create pictures of the inside of the body. Engineering osteoblastic metastases to delineate the. Bone metastases are common in patients with advanced malignancies.
However, osteoblastic bone metastases, such as those commonly encountered in prostate cancer, are still classified as nonmeasurable and cannot be assessed. Cancer cell volume and shape factor were obtained from imaris imaging analysis software version 9. We demonstrate nir lightbased detection of osteoblastic activity in the living animal and discuss how this technology can be used to study skeletal development, osteoblastic metastasis. Prostate cancer cells promote osteoblastic bone metastases.
Most skeletal metastases are primarily osteolytic or mixed osteolytic osteoblastic, whereas some are sclerotic. Osteoblastic metastases distinguished from enostoses using. Monitoring of osteosarcoma radiation treatment effectiveness was performed with bone, ct, mri and petct fusion imaging. There is currently no imaging biomarker for metastatic prostate cancer. Osseous metastatic disease can be osteolytic, osteoblastic, or mixed. Osteoblastic metastases distinguished from enostoses using ct. Indeed, bone is the third most common organ affected by metastasis, surpassed only by the lungs and liver24, and is the most common site of distant metastasis from primary breast carcinoma. Multiple osteoblastic metastases to the pelvis and lumbar vertebral bodies from carcinoma of the prostate note discrete rounded sclerotic lesions in right ilium and ivory vertebra involving l4 and s1. Jan 27, 2017 our temporal 3d ct subtraction cad software easily detected vertebral metastases on the followup ct images of lung cancer patients regardless of the osteolytic or osteoblastic nature of the lesions, wrote dr. Sensitivities, specificities, and positive and negative predictive values with corresponding confidence intervals were calculated for the detection of osteoblastic rib lesions using an advanced postprocessing package enabling inplane rib reading in ctimages screening and diagnostic accuracy were calculated separately. Osseus metastases from kidney, thyroid and lung maligancies are predominantly osteolytic, while osteoblastic lesions are usually seen in prostate cancer and breast cancer. Confocal imaging of the hotecs demonstrated that col1 and fn were highly expressed in the.
Morphology of bone metastases should guide treatment in. In osteolytic bone metastasis, a complicated molecular interaction called. Xrays can also show fractures breaks in bones that have been weakened by metastases. If mri was the initial imaging examination and spine metastases were.
Improved detection of bone metastases from lung cancer in the. It allows for appropriate measures to be taken to prevent complications and improve quality of life. On a later ct scan of the invisible patient, the osteoblastic lesion has been developed. Roughly four in five patients with bone metastatic breast or prostate cancer. Conclusion our temporal 3dct subtraction cad software easily detected vertebral metastases on the followup ct images of lung cancer patients regardless of the osteolytic or osteoblastic nature of the lesions. Osseus metastases from kidney, thyroid and lung maligancies are predominantly osteolytic, while osteoblastic lesions are usually seen in. Molecular imaging of bone metastasis human health campus. Metastasis of malignant neoplasms to bone is common with metastases being far more prevalent than primary bone malignancies1,2. Often, bone metastases have both lytic and blastic features. The mechanisms responsible for tumor growth in bone are complex and involve tumor stimulation of the osteoclast and the osteoblast. Osteoblastic metastases prostate carcinoma radiology case. To evaluate the effect of ct software that generates rib unfolding images and. Osteoblasts are educated by crosstalk with metastatic breast. Comparison of wholebody mri and bone scintigraphy in the.
Moreover, numbering ribs and thoracic spines in chest ct is time consuming and exhausting. Samarium153 lexidronam 153 smedtmp is fda approved for painful osteoblastic bone metastases that image on bone scan. We retrospectively assessed the ctdata of 60 consecutive prostate cancer patients by applying dedicated software enabling inplane rib reading. Zoledronic acid inhibits both the osteolytic and osteoblastic. Imaging bone metastases is problematic because the lesions can be osteolytic, osteoblastic, or mixed, and imaging modalities are based on either direct anatomic visualization of the bone or tumor or indirect measurements of bone or tumor metabolism. Detection of rib metastases in patients with lung cancer. A multigenic program mediating breast cancer metastasis to bone. Imaging bone metastases is problematic because the lesions can be osteolytic, osteoblastic, or mixed, and imaging modalities are based on either direct anatomic visualization of the bone or tumor. Differentiating osteopoikilosis from osteoblastic metastases. Autopsy series have shown an incidence of approximately 70% in breast and prostate cancer and 35% in lung cancer. Certain solid tumors metastasize to bone and cause osteolysis and abnormal new bone formation. Bone metastases in breast cancer may be osteolytic, osteoblastic, or mixed blastic and lytic. Quantified using volocity 3d image analysis software, the time. Imaging tests may be done before, during, and after cancer.
Wnts are a large family of proteins that promote bone growth. Osteoblastic metastases exhibit low signal not only on t1 but also on t2weighted mr images, but also on stir. It can be divided into bioluminescence imaging bli and fluorescence imaging fli. Based on reference standard, 78 metastatic bone lesions in 26. Uptake of an agent depends on the blood supply, the capillary to bone transfer through extra cellular space and the degree of osteoblastic and. Jan 24, 2018 metastases from carcinoma are by far the most common malignant tumors involving the skeleton. Samarium for osteoblastic bone metastases and osteosarcoma. Accuracy of ct attenuation measurement for differentiating treated osteoblastic metastases from enostoses original research.
Although bone metastases can be treated, their response to treatment is considered. Effect of bone reading ct software on radiologist performance in. Evaluating the effects of mixed osteolyticosteoblastic. Computed tomography ct imaging can determine whether lesions are osteolytic, osteoblastic, or mixed. Differentiation of predominantly osteoblastic and osteolytic spine. On xrays, these changes show up as spots that are whiter than the bone around them. In other words, we showed clinically that bm metastasis is an early stage of bone metastasis that is detected by f18fdgpet but not by ct. They must be included in any differential diagnosis of a bone lesion in a patient older than 40 years. Our temporal 3d ct subtraction cad software easily detected vertebral metastases on the followup ct images of lung cancer patients regardless of the osteolytic or osteoblastic nature of the lesions, during routine interpretation of a thoracic ct image for followup of primary lung cancer, iwano and colleagues wrote. Diagnostic performance of a computerassisted diagnosis system for.
Human khos or krib os cells, tagged or untagged with a luciferase reporter construct, were transplanted directly into the tibial cavity of nude mice. The rationale of using hybrid techniques for bone metastasis imaging is the assessment of complimentary information, e. The importance of recognizing osteopoikilosis lies in differentiating it from osteoblastic metastases. This retrospective study showed clinically by 18ffdg petct imaging that bm metastasis is an early stage of bone metastasis in breast cancer. Bone metastasis cancer cells that break off from a primary tumor and enter the bloodstream or lymph. Apart from a pathological diagnosis, radiological diagnosis is the most common approach to locating metastatic spread. Sixtyfive percent of bm metastases had converted into bone metastases after treatment. Accuracy of ct attenuation measurement for differentiating. Osteoblastic metastases are most often associated with prostate and breast. The phenotypes have different effects on bones and may in.
Reading the conventional multiplanar reconstructions was. Hypocalcemia with osteoblastic metastases in a patient with prostate carcinoma. Diagnostic imaging modalities of osteoblastic metastases. We identified patients with treated osteoblastic metastases using the same search terms as those used for untreated osteoblastic metastases, but we chose patients who had a history of systemic chemotherapy or antiandrogen therapy of at least 3 months. Median overall survival after a diagnosis of bone metastases, which occurred on average 2. Therefore, using bone reading software in breast cancer can be very helpful for improving radiologist performance particularly in the. Imaging has an important role in the detection, diagnosis, prognostication, treatment planning, and followup monitoring of bone metastases. Contemporary approaches for imaging skeletal metastasis ncbi. Ct scans depicted osteoblastic changes in eight patients 16 osteoblastic metastatic lesions, osteolytic changes in seven 16 osteolytic metastatic lesions, and mixed changes in 12. Wnt activity is antagonized by endogenous proteins including dickkopf1 dkk1.
Thus, osseous metastases can be osteoblastic bone forming or osteolytic bone destructive, however, a combination of both processes occurs in most cancers. Apart from the rather blastic or lytic appearance, functional and metabolic characteristics are further influenced by the primary tumor entity. Frontal x ray of pelvis with diffuse, coarse, patchy areas of hyperdensity noted in the visualized bones. One of the factors that might be involved in prostatic bone lesions is the growth factor endothelin1 et1, which is produced by prostate cancer cells. Automated image analysis software has been shown to significantly. Imaging plays a major role in detection, followup, and molecular. Interest is increasing in the role of the osteoblasts in bone metastases, and it has recently been established that the wnt signaling system plays a key role in bone development and turnover. Osteoblastic lesion screening with an advanced post.
Secondary osseous involvement in lymphoma is more common compared to primary bone lymphoma. Engineering osteoblastic metastases to delineate the adaptive. No large studies are available to discuss the effect of breast cancer histologic subtype on the multimodality imaging detection of bone metastases. This study showed by clinical molecular imaging that osteolytic and osteoblastic metastatic bone lesions were preceded by bone marrow metastases.
In lytic lesions, structural integrity is often impaired, potentially warranting surgical reconstruction, while blastic lesions incite bone formation and may contribute to cord. Considering the dominant role of osteoblasts in prostate cancer. Furthermore, osteolytic metastases tend to be aggressive, whereas sclerotic metastases typically demonstrate slower progression. Molecular and functional imaging of bone metastases in breast and prostate cancers. To evaluate the efficacy of zoledronic acid zol against osteosarcoma os growth, progression, and metastatic spread using an animal model of human os that closely resembles the human disease. Within the cohort, 43 patients died during followup. The respective phenotypes of dysregulated bone destruction and bone formation represent two ends of a spectrum, and most patients will have evidence of both. Vertebral metastases represent the secondary involvement of the vertebral spine by haematogenouslydisseminated metastatic cells. Fdg avid breast cancer bone metastases silent on ct and. Wnt activity is antagonized by endogenous proteins including dickkopf1.
While imaging has become an integral part of diagnosing patients presenting with malignancy, it can be confusing when an osteoblastic lesion is identified in the presence and absence of a. However, this distinction is not absolute, and many patients have a mixed picture of both osteolytic and osteoblastic metastases. The frequency of osteolytic bone metastasis is determined by. A total of 64 metastases 38 predominantly osteoblastic, 26 predominantly osteolytic were detected. The recent development of agents that target the osteolytic components of bone metastasis, including bisphosphonates and denosumab, showed promising results in osteolytic bone diseases such as multiple myeloma but were less effective in improving the osteoblastic bone disease found in prostate cancer. Bone metastases can involve any skeletal site, but the spine and the ribs are most frequently impacted as they represent the reservoir of hematopoietic bone marrow in adults, which is known to be better vascularized 3, 5. Bm metastasis was considered if the lesion was pet positivect occult while bone. Twelve percent of bm metastases had persisted after treatment. The authors report a case of metastatic breast carcinoma that on investigation was shown to have a negative bone scan in spite of multiple densely sclerotic metastases on radiography and ct and a positive bone biopsy. Furthermore, recent hardware and software advances have led to.
Osteolytic metastasis is the most common form of bone metastasis in all cancer patients. Bone metastases are considered a form of advanced cancer. Effects of breast cancer cells on osteoblasts were recapitulated in vitro by. Spine metastases involving only the bone marrow, endplate or posterior element are difficult to be detected on ct. Bone marrow metastasis is an early stage of bone metastasis in. Reading the conventional multiplanar reconstructions was considered to be. Quantitative assessment of bone metastasis in prostate. Distinguishing untreated osteoblastic metastases from. The most common primary tumor to cause osteoblastic metastases is prostate cancer, followed closely by breast cancer. The present study shows that our temporal 3dct subtraction cad software can help radiologists to detect vertebral metastases, regardless of the osteolytic or osteoblastic nature of the lesions, during routine interpretation of a thoracic ct image for followup of primary lung cancer. Radiographic findings are diagnostic, and the disease often is discovered incidentally on xray films.
Bone is a metabolically active tissue undergoing remodelling in relation to stress and strain with osteoblastic repair and osteoclastic removal of bone. Imaging findings suggestive of a particular primary tumor. In our study, the goal was to see whether the use of traditional bone scanning for detection of bone metastases in breast cancer is better than that of 18 ffdg pet. Hypocalcemia with osteoblastic metastases in a patient with. Imaging characteristic analysis of metastatic spine. The finding of osseous lesion can be incidentally discovered during the course of the disease. Contemporary approaches for imaging skeletal metastasis bone. Methods are emerging to improve the imaging of skeletal metastasis.
Osteopoikilosis is a rare, benign osteosclerotic dysplasia that predominantly involves the appendicular skeleton. Imaging metastatic bone disease from carcinoma of the. Monitoring tumor metastases and osteolytic lesions with. Sep 29, 2009 imaging bone metastases from prostate cancer presents several challenges. Although mature mice presented with fewer overt bone metastases, the. Preclinical cancer research optical imaging modalities optical imaging is based on the detection of photons emitted from living cells, tissues or animals. Nuclear medicine imaging in bone metastases cancer. In bone metastases that are predominantly osteolytic, parathyroid. Bone metastases are tumors that occur when cancer cells break away from the place where they started growing and move into bone tissue. Apart from a pathological diagnosis, radiological diagnosis is the most common approach to locating metastatic.
Microenvironment engineering of osteoblastic bone metastases reveals osteomimicry of patientderived prostate cancer xenografts. Although bone metastases can be treated, their response to treatment is considered unmeasurable. Both readers detected more osteolytic and osteoblastic metastases with cad than without cad. Statistical analysis was performed with statistical software r version 3. The lesions are usually sclerotic and appear late on the conventional xray. Osteoblastic or blastic metastases cause an area of the bone to look denser or sclerotic. The detection of bone metastases in a patient with cancer will alter the treatment plan.
Images were colored in postprocessing by staking to a single rgb image using imagej software 1. In lytic lesions, structural integrity is often impaired, potentially warranting surgical reconstruction, while blastic lesions incite bone formation and may contribute to cord compression requiring decompression. Thoracic temporal subtraction three dimensional computed. N2 samarium153 lexidronam 153smedtmp is fda approved for painful osteoblastic bone metastases that image on bone scan. Apr 25, 2019 a threedimensional model of prostate tumor cells growing in a bonelike microenvironment offers a new platform for studying how metastatic prostate cancers respond to therapies.
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