Introduction Bone marrow is the fourth largest organ of the human body. Its main function is the hematopoiesis, i.e., it provides the body with erythrocytes, leukocytes and platelets in order to maintain the oxygenation, immune function and auto-restoration of the body. MR imaging provides a non-invasive visualization of the bone marrow and may be used to define its cellular or fat content as well as its vascularity and metabolism. Treatment effects due to irradiation, chemotherapy or other new treatment regimens may change one or several of these components, thereby causing local or generalized changes in bone marrow signal intensity on MR images. This article will provide an overview over such treatment-related bone marrow signal changes on MR imaging. In order to recognize these treatment effects, one has to be familiar with the MR imaging features of the normal and non-treated pathologic marrow. Thus, this article will first provide a brief overview over MR imaging features of the normal and non-treated pathologic marrow as a basis for subsequent descriptions of the bone marrow after conservative or new treatments. Indications to study treatment effects 1 2 4 2 3 4 5 6 7 8 9 10 11 12 3 4 12 12 13 12 14 In summary, dedicated MR imaging of the bone marrow in patients with hematologic malignancies is currently restricted to applications in patients with multiple myeloma, selected patients with other malignant lymphomas with a high risk of bone marrow infiltration and/or extracompartmental tumor growth as well as patients with potential treatment complications. Additional patients with hematologic malignancies may undergo MR imaging for evaluations of other pathologies, outside the bone marrow. And since the bone marrow is depicted on nearly any MR examination throughout the body, the knowledge of the normal and pathologic marrow of these patients before and after therapy is crucial for the radiologist in order to provide a comprehensive diagnosis. Such “secondary” evaluations of the bone marrow may outperform above mentioned primary indications in this patient population. Technique Standard techniques 15 18 18 18 19 20 21 Contrast-agent enhanced scans non non non 22 23 23 24 26 27 27 28 30 17 29 31 17 17 31 32 New developments for whole body MR imaging, such as parallel imaging techniques, dedicated coils (Angio-SURF), and the total imaging matrix (Siemens systems, Avanto) may provide a “screening” of the whole red bone marrow for tumor infiltration within a reasonable time. 33 34 Normal bone marrow 35 38 38 38 38 26 25 Pathologic bone marrow in hematologic malignancies Neoplastic infiltration of the bone marrow in MR images results in a replacement of the fatty converted marrow by neoplastic cells, thereby increasing the cellular content of the bone marrow, which results in a prolongation of T1- and T2-relaxation times and subsequent decreased T1-signal and increased T2-signal of the bone marrow. The detection of neoplastic bone marrow infiltrations with MR imaging depends on the quantity and distribution of cellular infiltration. The distribution of neoplastic bone marrow involvement in patients with hematologic malignancies may be focal, multifocal or diffuse. In patients with NHL, a focal or multifocal involvement is more common than the diffuse infiltration pattern. In patients with myeloma, an additional, typical “salt and pepper” or variegated distribution may be observed, most frequently in stage I disease according to Salmon and Durie. In patients with leukemia, the bone marrow is usually involved in a diffuse fashion. A multifocal involvement may be seen in a small proportion of patients, particularly those with AML. The detection of focal, multifocal and “salt and pepper” or variegated infiltrations of the bone marrow in patients with NHL is straight forward: The MR signal intensity of focal bone marrow lesions is typically iso- or hypointense to surrounding muscle and intervertebral disks on T1-weighted MR images and hyperintense to surrounding muscle on STIR- or fat saturated T2-weighted MR images. Since these focal lesions are also associated with an increased angiogenesis, they show an increased signal enhancement compared to the surrounding bone marrow on fat saturated T1-weighted MR images. 39 40 22 23 41 42 43 Irradiation 1 44 Fig. 1 a b  45 46 47 47 47 47 47 2 Fig. 2 a b c  48 49 48 50 51 Cortisone treatment 3 4 47 Fig. 3 a b  Fig. 4 a b c  AVN is caused by vascular insufficiency, compromised bone marrow perfusion, and, finally, anoxia and death of bone marrow cells. Bones with end-arterial vascular supply and poor collaterals are particularly prone to develop an AVN, such as the femoral head, distal femur and proximal tibia, proximal humeri, tali, scaphoid, and lunate bones. Usually, the cartilage is not affected because it is nourished by synovial fluid. 52 53 54 53 54 There is currently no established role for Gd-administration in non-traumatic AVN. Of note, in children, the proximal femur epiphyses may show a residual, small subcortical rim of hematopoietic marrow, which typically appears brighter than adjacent muscles on plain T1-weighted MR images. This should not be confused with the “double line sign” in early AVN, which is characterized by a subcortical rim, which is iso- or hypointense compared to surrounding muscle. 52 55 Chemotherapy 56 58 5 Fig. 5 a b  59 60 6 60 6 58 60 7 61 60 Fig. 6 a c b d a b c d  Fig. 7 a a b c e  58 62 63 22 23 41 64 65 Bone marrow reconversion after standard therapy After successful cytotoxic therapy and/or irradiation, the normal bone marrow may undergo a reconversion from fatty to highly cellular hematopoietic marrow. This reconversion occurs in a reverse fashion compared to the conversion from hematopoietic marrow to fatty marrow, described above, i.e., the reconversion progresses from the central skeleton to the periphery. Within long bones, it involves first the metaphyses and then the diaphyses. The presence of cellular marrow within the epiphyses in an adult patient with hematologic malignancies is always suspicious for neoplastic infiltration, especially when the rest of the bone marrow did not undergo a complete reconversion. A reconversion of marrow within the epiphyses is only rarely seen, usually in conjunction with an extensive reconversion of the hematoietic marrow of the whole bone. 66 67 8 66 68 Fig. 8 a b c  69 71 72 73 17 29 31 8 9 17 29 31 10 10 Fig. 9 a b c 31  Fig. 10 a b c 31  New therapy regimens 74 75 76 76 77 78 79 Stem cell transplantation The most commonly used therapy for patients with lymphoma is autologous stem cell transplantation. For this, the patient receives a conditioning therapy, then his or her own stem cells are collected by leukapheresis, the patient subsequently receives a high-dose chemotherapy or irradiation and his previously collected stem cells are reinfused. With some types of lymphoma, an autologous transplant may not be possible in case of persistent malignant bone marrow infiltration. Even after purging (treatment of the stem cells in the lab to kill or remove lymphoma cells), reinfusion of some lymphoma cells with the stem cell transplant is possible. It would, therefore, be of high clinical significance to be able to differentiate patients with still viable lymphoma cells in their bone marrow at the time of leukapheresis from patients in true complete remission. In refractory diseases or in aplastic anemia, allogenic marrow transplantation or chord cell transplantation are also used. This much more aggressive procedure is initiated by a conditioning high dose chemotherapy and/or total body irradiation and subsequent reinfusion of allogenic donor cells, i.e., stem cells from a matched sibling or unrelated donor. Allogenic transplantation has limited applications, because of the need for a matched donor. Another drawback is that side effects of this treatment are too severe for most people over 55 years old. After the conditioning therapy for allogenic marrow transplantation, the patients reach complete aplasia, are usually isolated on a bone marrow transplantation unit and should only undergo MR imaging for vital indications. 80 17 81 80 82 83 82 83 84 11 85 80 Fig. 11 Patient with malignant lymphoma after TBI and bone marrow transplantation: Plain T1-w MR image (center) shows residual hypointense bone marrow lesions in the pelvis and proximal femur. Some of these lesions may be residual marrow abnormalities of uncertain significance. Other lesions, such as the serpiginous lesions in both proximal femurs represent therapy-induced bone infarcts. These lesions show a corresponding serpiginous hyperintense area on STIR images (left) and a minor, serpiginous enhancement on Gd-enhanced T1-w scans (right)  12 86 Fig. 12 A patient with myeloma after bone marrow transplantation: The bone marrow of the lumbar spine shows a diffuse hypointense signal intensity on both plain T1-weighted (left) and fat-saturated T2-weighted (right) MR images  11 In summary