Posted in Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, mesenteric ischemia, MRI, Vascular Diseases on December 26, 2015| Leave a Comment »
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Posted in Biomedical Measurement Science, Cancer and Current Therapeutics, Cancer Screening, Clinical & Translational, Clinical Diagnostics, Curation, Diagnostics and Lab Tests, Genome Biology, History and physical exam, Human Immune System in Health and in Disease, Image Processing/Computing, Imaging-based Cancer Patient Management, Immunodiagnostics, Methods, Molecular Genetics & Pharmaceutical, MRI, Personalized and Precision Medicine & Genomic Research, Population Health Management, tagged breast cancer, limitations, mammography on November 8, 2015| Leave a Comment »
Dense Breast Mammogram
Larry H. Bernstein, MD, FCAP, Curator
LPBI
The Problem With Mammograms
http://forward.com/culture/324003/the-problem-with-mammograms/#ixzz3queBnx00
Hallie Leighton had dense breasts — a fact she discovered only in her late 30s, via a mammogram. She grew up in an Ashkenazi family in New York, pursued a career in writing and worked with organizations promoting peace between Israelis and Arabs. By 2013 she was making a documentary on her father Jan Leighton, an actor who set the record as an actor for appearing in the most roles (2,407 according to the 1985 Guinness Book of World Records). She was never able to complete it. She died that year, at the age of 42.
Every woman in Leighton’s family had breast cancer, so she began getting annual mammograms at 35 — five years earlier than the recommended age. In 2009 the results of Leighton’s mammogram came in as “negative” or “normal”; by 2013 she was bedridden, undergoing her final days of chemotherapy.
When Leighton was first diagnosed in 2010, her doctor told her, “You have breast cancer, and it was there in 2009.” The tumor in Leighton’s breast went undiscovered until it was palpable — and at that point, the cancer was already in stage 4.
“Happygram,” a documentary which exposes some of the shortcomings in mammography, chronicles Leighton’s struggle with cancer and the implications of having dense breasts.
“Most women simply aren’t informed that they have dense breast tissue,” said Leighton’s best friend Julie Marron. She wrote and directed the documentary, which is currently screening at film festivals around the country.
Breast density is defined by the relative amount of fat in relation to the amount of connective and epithelial tissue (tissue that lines blood vessels and cavities). When more than 50% of breast tissue is connective and epithelial tissue, instead of fatty tissue, the breasts are considered dense. Mammography is the only way to determine breast density.
“If you have dense breasts, what looks dense on a mammogram looks the same as a cancer would look. It tends to confuse or confound the physician, and reduces the sensitivity of the mammogram,” said Gerald Kolb, founder and president of The Breast Group, which counsels clients on different technologies in breast care. “Hallie Leighton’s breasts looked like snowballs; there was no chance they were going to find anything with the mammogram.”
Forty percent of women who are screened for breast cancer have dense breast tissue. These women also account for more than 70% of all invasive cancers. “Mammograms are not very effective screening tools for these women, as they miss between 50% and 75% of all invasive cancers in dense breast tissue,” Marron said. “This is obviously a very critical issue when you are dealing with a population that is more likely to develop cancer.”
Ashkenazi women are even more at risk. They are 1.6 times more likely than the general population to have dense breast tissue, according to Kolb. Moreover, one in 40 Ashkenazi women will test positive for one or both of BRCA gene mutations responsible for breast cancer. For the general population, that number is between one in 350 and one in 800.The BRCA 1 or 2 genes don’t cause cancer, they fight cancer, Kolb says. But if the gene is mutated, the body is not as well equipped to fight the cancer.
“A woman with a BRCA mutation has a lifetime risk of around 33% to 87%, depending on the gene and mutation,” Marron said. “Compare this to a lifetime risk of 12% for developing breast cancer for the overall population.” BRCA gene mutations can be inherited from either or both parents, and therefore they can be present in men as well as in women.
Breast density and BRCA gene mutations are not directly related, but both independently present an increased susceptibility to breast cancer.
“The biggest risk is that a doctor is not going to find the cancer when it’s really small,” Kolb said. When a tumor is detected at a centimeter or smaller, there’s a 95% cure rate. But if the cancer is the size of a golf ball by the time it’s detected, Kolb says, the woman has a 60% chance of living for five years, and then her mortality increases dramatically.
The good news is that mammography isn’t the only method of detecting breast cancer; the bad news is that very few people know this. “What we’re trying to do in the density movement is give women enough information so they can ask appropriate questions of a doctor,” Kolb said.
Kolb advises high-risk women to get a genetic risk analysis, which can be performed by a genetic counselor or a radiologist. He advises getting the risk analysis as early as age 25, but doing so is a personal decision. Not every woman is emotionally prepared to know the results.
“Mammography is a starting point,” said Dr. Dennis McDonald, a California-based women’s imager. Additionally, doctors recommend that women with dense breasts get an MRI, which McDonald says is reserved for high-risk women. It’s an expensive, invasive and time-consuming procedure that requires the injection of fluid in order to read the MRI. As of yet, doctors do not know the side effects of getting an annual MRI.
“A doctor should have started [Leighton] on an MRI right away. She was high risk and they chose to just monitor with a mammogram,” Kolb said. “That’s insufficient.”
Breast ultrasound is another alternative for women with dense breast tissue. “Most of the time, breast density doesn’t present a problem [with ultrasounds],” McDonald said. Though the ultrasound is effective in detecting cancer, he says the downside is that radiologists are often not that comfortable with the technology, simply because they have little experience with it. There are also a lot of false positives, he adds, which result in unnecessary exams or biopsies.
As “Happygram” documents, informing women of their breast density and of alternatives to mammography is a highly charged political issue.
“The whole breast cancer industry has grown up around mammograms,” Marron said. “Physicians weren’t educated on [breast density], deliberately so to a certain extent, and refused to inform patients on this issue, which is really outrageous if you think about it.” Marron says that doctors are required by law and ethical guidelines to inform patients of “material” medical information. “There is no legitimate reason that women have not been informed of this information,” she noted.
After Leighton’s diagnosis, she wanted to ensure that other women didn’t suffer the same misfortune of all-too-late tumor discovery on account of dense breast tissue. She gave media interviews, lobbied in Albany and starred in “Happygram,” all the while undergoing chemotherapy. She died four months after the Breast Density Information Bill passed in New York.
The law requires that every mammography report given to a patient with dense breasts inform the patient in plain language that she has dense breast tissue and that she should talk to her physician about the possible benefits of additional screenings. In New York, the first state in the nation to pass this kind of law, at least 2,500 women with dense breasts and invasive breast cancer received “normal” or “negative” results on their mammograms.
Similar legislation has been passed in more than 20 states throughout the country, but not without objection. Many well-intentioned radiologists, poorly informed about alternative screening options, feared that telling women the limitations of mammography would cause them to lose faith in it altogether and not get tested. Others argued that the information would make women anxious, and that it wouldn’t be fair for those who couldn’t afford additional testing. And still further arguments against informing women were possibly impacted by financial considerations, Marron added.
“Women aren’t getting the benefit of full notification across the board yet,” Marron said. “I think that has to change through education. That’s the primary reason we made this movie. There’s been so much resistance within the medical community to telling women. Change isn’t going to come from the medical community, it has to come from the patients.”
Ashkenazi women shouldn’t panic, Kolb says, but they need to carefully examine their breast density and alternative screening options: “Anytime you have a preventative tragedy like that, you have to do everything in your power to stop it from happening.”
Madison Margolin is a freelance writer based in New York. She writes frequently for the Village Voice.
Read more: http://forward.com/culture/324003/the-problem-with-mammograms/#ixzz3qufQOSmn
Posted in MRI, Mutant Gene Expression, Neuroscience, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Schizophrenia, tagged corpus callosum, Neuroimaging, Schizophrenia on October 27, 2015| Leave a Comment »
Schizophrenia Brain
Larry H. Bernstein, MD, FCAP, Curator
LPBI
Neuroimaging studies using fMRI and PET to examine functional differences in brain activity in patients with schizophrenia have shown that differences seem to most commonly occur in the frontal lobes, hippocampus, and temporal lobes. These differences are heavily linked to the neurocognitive deficits which often occur with schizophrenia, particularly in areas of memory, attention, problem solving, executive function and social cognition.
Earlier studies from the researchers reported evidence suggesting that schizophrenia is not a single disease but a group of eight genetically distinct disorders, each with its own set of symptoms. Results found that distinct sets of genes were strongly associated with particular clinical symptoms.
The current study investigates the brain’s anatomy and shows that there are distinct subgroups of patients with a schizophrenia diagnosis that correlates with symptoms. This also explains the difficulty in past studies to identify a single set of biomarkers for a single type of schizophrenia.
The current study evaluated scans taken with magnetic resonance imaging (MRI) and a technique called diffusion tensor imaging in 36 healthy volunteers and 47 people with schizophrenia. Results show that the scans of patients with schizophrenia had various abnormalities in portions of the corpus callosum, a bundle of fibers that connects the left and right hemispheres of the brain and is considered critical to neural communication. Characteristics across the corpus callosum revealed in the brain scans matched specific symptoms of schizophrenia. Patients with specific features in one part of the corpus callosum typically displayed bizarre and disorganized behaviour. In other patients, irregularities in a different part of that structure were associated with disorganized thinking and speech and symptoms such as a lack of emotion; other brain abnormalities in the corpus callosum were associated with delusions or hallucinations. The lab conclude that their findings provide further evidence that schizophrenia is a heterogeneous group of disorders rather than a single disorder.
The team surmise that they didn’t start with people who had certain symptoms and then look to see whether they had corresponding abnormalities in the brain. They note that they just looked at the data, and the patterns began to emerge. They go ony to add that this kind of granular information, combined with data about the genetics of schizophrenia, one day will help physicians treat the disorder in a more precise way.
Many genes responsible for the creation of synaptic proteins have previously shown to be strongly linked to schizophrenia and other brain disorders, however, until now the reasons have not been understood. Now, researchers from Cardiff University have identified a critical function of what they believe to be schizophrenia’s ‘Rosetta Stone’ gene that could hold the key to decoding the function of all genes involved in the disease. The team state that the breakthrough has revealed a vulnerable period in the early stages of the brain’s development that they hope can be targeted for future efforts in reversing schizophrenia. The study is published in the journal Science.
The gene identified in the current study is known as ‘disrupted in schizophrenia-1’ (DISC-1). Earlier studies have shown that when mutated, the gene is a high risk factor for mental illness including schizophrenia, major clinical depression and bipolar disorder. The aim of the current study was to determine whether DISC-1’s interactions with other proteins early on in the brain’s development had a bearing on the brain’s ability to adapt its structure and function, also known as ‘plasticity’, later on in adulthood.
In order for healthy development of the brain’s synapses to take place, the DISC-1 gene first needs to bind with two other molecules known as ‘Lis’ and ‘Nudel’. The experiments in mice revealed that by preventing DISC-1 from binding with these molecules prevents cortical neurons in the brain’s largest region from being able to form synapses. The ability to form coherent thoughts and to properly perceive the world is damaged as a consequence of this.
Preventing DISC-1 from binding with ‘Lis’ and ‘Nudel’ molecules when the brain was fully formed had no effect on its plasticity. However, the researchers were able to pinpoint a seven-day window early on in the brain’s development, one week after birth, where failure to bind had an irreversible effect on the brain’s plasticity later on in life.
The researchers hypothesize that DISC-1 is schizophrenia’s Rosetta Stone gene and could hold the master key to help unlock the understanding of the role played by all risk genes involved in the disease. They go on to add that they have identified a critical period during brain development that will assist in testing whether other schizophrenia risk genes affecting different regions of the brain create their malfunction during their own critical period.
Posted in Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, CT, Image Processing/Computing, Imaging-based Cancer Patient Management, MRI, Personalized and Precision Medicine & Genomic Research, Radio Frequency (RF)-based Surgical Solutions, Ultra Sound, tagged Cancer - General, Cancer Surgery, cancer treatment, Clinical trial, FDG PET, imaging, Medical imaging, Personalized medicine, PET, PET/MRI, Prostate cancer, robotic surgery, surgery, ultrasound based cancer detection on August 5, 2015| Leave a Comment »
The advent of medical-imaging technologies such as image-fusion, functional-imaging and noninvasive tissue characterisation is playing an imperative role in answering this demand thus transforming the concept of personalized medicine in cancer into practice. The leading modality in that respect is medical imaging. To date, the main imaging systems that can provide reasonable level of cancer detection and localization are: CT, mammography, Multi-Sequence MRI, PET/CT and ultrasound. All of these require skilled operators and experienced imaging interpreters in order to deliver what is required at a reasonable level. It is generally agreed by radiologists and oncologists that in order to provide a comprehensive work-flow that complies with the principles of personalized medicine, future cancer patients’ management will heavily rely on computerized image interpretation applications that will extract from images in a standardized manner measurable imaging biomarkers leading to better clinical assessment of cancer patients.
As consequence of the human genome project and technological advances in gene-sequencing, the understanding of cancer advanced considerably. This led to increase in the offering of treatment options. Yet, surgical resection is still the leading form of therapy offered to patients with organ confined tumors. Obtaining “cancer free” surgical margins is crucial to the surgery outcome in terms of overall survival and patients’ quality of life/morbidity. Currently, a significant portion of surgeries ends up with positive surgical margins leading to poor clinical outcome and increase of costs. To improve on this, large variety of intraoperative imaging-devices aimed at resection-guidance have been introduced and adapted in the last decade and it is expected that this trend will continue.
The Status of Contemporary Image-Guided Modalities in Oncologic Surgery is a review paper presenting a variety of cancer imaging techniques that have been adapted or developed for intra-operative surgical guidance. It also covers novel, cancer-specific contrast agents that are in early stage development and demonstrate significant promise to improve real-time detection of sub-clinical cancer in operative setting.
Another good (free access) review paper is: uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery
Pre- and intraoperative diagnostic techniques facilitating tumor staging are of paramount importance in colorectal cancer surgery. The urokinase receptor (uPAR) plays an important role in the development of cancer, tumor invasion, angiogenesis, and metastasis and over-expression is found in the majority of carcinomas. This study aims to develop the first clinically relevant anti-uPAR antibody-based imaging agent that combines nuclear (111In) and real-time near-infrared (NIR) fluorescent imaging (ZW800-1). Conjugation and binding capacities were investigated and validated in vitro using spectrophotometry and cell-based assays. In vivo, three human colorectal xenograft models were used including an orthotopic peritoneal carcinomatosis model to image small tumors. Nuclear and NIR fluorescent signals showed clear tumor delineation between 24h and 72h post-injection, with highest tumor-to-background ratios of 5.0 ± 1.3 at 72h using fluorescence and 4.2 ± 0.1 at 24h with radioactivity. 1-2 mm sized tumors could be clearly recognized by their fluorescent rim. This study showed the feasibility of an uPAR-recognizing multimodal agent to visualize tumors during image-guided resections using NIR fluorescence, whereas its nuclear component assisted in the pre-operative non-invasive recognition of tumors using SPECT imaging. This strategy can assist in surgical planning and subsequent precision surgery to reduce the number of incomplete resections.
INTRODUCTION
Diagnosis, staging, and surgical planning of colorectal cancer patients increasingly rely on imaging techniques that provide information about tumor biology and anatomical structures [1-3]. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are preoperative nuclear imaging modalities used to provide insights into tumor location, tumor biology, and the surrounding micro-environment [4]. Both techniques depend on the recognition of tumor cells using radioactive ligands. Various monoclonal antibodies, initially developed as therapeutic agents (e.g. cetuximab, bevacizumab, labetuzumab), are labeled with radioactive tracers and evaluated for pre-operative imaging purposes [5-9]. Despite these techniques, during surgery the surgeons still rely mostly on their eyes and hands to distinguish healthy from malignant tissues, resulting in incomplete resections or unnecessary tissue removal in up to 27% of rectal cancer patients [10, 11]. Incomplete resections (R1) are shown to be a strong predictor of development of distant metastasis, local recurrence, and decreased survival of colorectal cancer patients [11, 12]. Fluorescence-guided surgery (FGS) is an intraoperative imaging technique already introduced and validated in the clinic for sentinel lymph node (SLN) mapping and biliary imaging [13]. Tumor-specific FGS can be regarded as an extension of SPECT/PET, using fluorophores instead of radioactive labels conjugated to tumor-specific ligands, but with higher spatial resolution than SPECT/PET imaging and real-time anatomical feedback [14]. A powerful synergy can be achieved when nuclear and fluorescent imaging modalities are combined, extending the nuclear diagnostic images with real-time intraoperative imaging. This combination can lead to improved diagnosis and management by integrating pre-intra and postoperative imaging. Nuclear imaging enables pre-operative evaluation of tumor spread while during surgery deeper lying spots can be localized using the gamma probe counter. The (NIR) fluorescent signal aids the surgeon in providing real-time anatomical feedback to accurately recognize and resect malignant tissues. Postoperative, malignant cells can be recognized using NIR fluorescent microscopy. Clinically, the advantages of multimodal agents in image-guided surgery have been shown in patients with melanoma and prostate cancer, but those studies used a-specific agents, following the natural lymph drainage pattern of colloidal tracers after peritumoral injection [15, 16]. The urokinase-type plasminogen activator receptor (uPAR) is implicated in many aspects of tumor growth and (micro) metastasis [17, 18]. The levels of uPAR are undetectable in normal tissues except for occasional macrophages and granulocytes in the uterus, thymus, kidneys and spleen [19]. Enhanced tumor levels of uPAR and its circulating form (suPAR) are independent prognostic markers for overall survival in colorectal cancer patients [20, 21]. The relatively selective and high overexpression of uPAR in a wide range of human cancers including colorectal, breast, and pancreas nominate uPAR as a widely applicable and potent molecular target [17,22]. The current study aims to develop a clinically relevant uPAR-specific multimodal agent that can be used to visualize tumors pre- and intraoperatively after a single injection. We combined the 111Indium isotope with NIR fluorophore ZW800-1 using a hybrid linker to an uPAR specific monoclonal antibody (ATN-658) and evaluated its performance using a pre-clinical SPECT system (U-SPECT-II) and a clinically-applied NIR fluorescence camera system (FLARE™).
Robotic surgery is a growing trend as a form of surgery, specifically in urology. The following review paper propose a good discussion on the added value of imaging in urologic robotic surgery:
With the development of novel augmented reality operating platforms the way surgeons utilize imaging as a real-time adjunct to surgical technique is changing.
A questionnaire was distributed via the European Robotic Urological Society mailing list. The questionnaire had three themes: surgeon demographics, current use of imaging and potential uses of an augmented reality operating environment in robotic urological surgery.
117 of the 239 respondents (48.9%) were independently practicing robotic surgeons. 74% of surgeons reported having imaging available in theater for prostatectomy 97% for robotic partial nephrectomy and 95% cystectomy. 87% felt there was a role for augmented reality as a navigation tool in robotic surgery.
This survey has revealed the contemporary robotic surgeon to be comfortable in the use of imaging for intraoperative planning it also suggests that there is a desire for augmented reality platforms within the urological community. Copyright © 2014 John Wiley & Sons, Ltd.
Since Röntgen first utilized X-rays to image the carpal bones of the human hand in 1895, medical imaging has evolved and is now able to provide a detailed representation of a patient’s intracorporeal anatomy, with recent advances now allowing for 3-dimensional (3D) reconstructions. The visualization of anatomy in 3D has been shown to improve the ability to localize structures when compared with 2D with no change in the amount of cognitive loading [1]. This has allowed imaging to move from a largely diagnostic tool to one that can be used for both diagnosis and operative planning.
One potential interface to display 3D images, to maximize its potential as a tool for surgical guidance, is to overlay them onto the endoscopic operative scene (augmented reality). This addresses, in part, a criticism often leveled at robotic surgery, the loss of haptic feedback. Augmented reality has the potential to mitigate this sensory loss by enhancing the surgeons visual cues with information regarding subsurface anatomical relationships [2].
Augmented reality surgery is in its infancy for intra-abdominal procedures due in large part to the difficulties of applying static preoperative imaging to a constantly deforming intraoperative scene [3]. There are case reports and ex vivo studies in the literature examining the technology in minimal access prostatectomy [3-6] and partial nephrectomy [7-10], but there remains a lack of evidence determining whether surgeons feel there is a role for the technology and if so for what procedures they feel it would be efficacious.
This questionnaire-based study was designed to assess first, the pre- and intra-operative imaging modalities utilized by robotic urologists; second, the current use of imaging intraoperatively for surgical planning; and finally whether there is a desire for augmented reality among the robotic urological community.
A web based survey instrument was designed and sent out, as part of a larger survey, to members of the EAU robotic urology section (ERUS). Only independently practicing robotic surgeons performing robot-assisted laparoscopic prostatectomy (RALP), robot-assisted partial nephrectomy (RAPN) and/or robotic cystectomy were included in the analysis, those surgeons exclusively performing other procedures were excluded. Respondents were offered no incentives to reply. All data collected was anonymous.
The questionnaire was created using the LimeSurvey platform (www.limesurvey.com) and hosted on their website. All responses (both complete and incomplete) were included in the analysis. The questionnaire was dynamic with the questions displayed tailored to the respondents’ previous answers.
When computing fractions or percentages the denominator was the number of respondents to answer the question, this number is variable due to the dynamic nature of the questionnaire.
All respondents to the survey were asked in what country they practiced and what robotic urological procedures they performed. In addition to what procedures they performed surgeons were asked to specify the number of cases they had undertaken for each procedure.
Procedure-specific questions in this group were displayed according to the operations the respondent performed. A summary of the questions can be seen in Appendix 1. Procedure-nonspecific questions were also asked. Participants were asked whether they routinely used the Tile Pro™ function of the da Vinci console (Intuitive Surgical, Sunnyvale, USA) and whether they routinely viewed imaging intra-operatively.
Before answering questions in this section, participants were invited to watch a video demonstrating an augmented reality platform during RAPN, performed by our group at Imperial College London. A still from this video can be seen in Figure 1. They were then asked whether they felt augmented reality would be of use as a navigation or training tool in robotic surgery.
Once again, in this section, procedure-specific questions were displayed according to the operations the respondent performed. Only those respondents who felt augmented reality would be of use as a navigation tool were asked procedure-specific questions. Questions were asked to establish where in these procedures they felt an augmented reality environment would be of use.
Of the 239 respondents completing the survey 117 were independently practising robotic surgeons and were therefore eligible for analysis. The majority of the surgeons had both trained (210/239, 87.9%) and worked in Europe (215/239, 90%). The median number of cases undertaken by those surgeons reporting their case volume was: 120 (6–2000), 9 (1–120) and 30 (1–270), for RALP, robot assisted cystectomy and RAPN, respectively.
When enquiring about the use of imaging for surgical planning, the majority of surgeons (57%, 65/115) routinely viewed pre-operative imaging intra-operatively with only 9% (13/137) routinely capitalizing on the TilePro™ function in the console to display these images. When assessing the use of TilePro™ among surgeons who performed RAPN 13.8% (9/65) reported using the technology routinely.
When assessing the imaging modalities that are available to a surgeon in theater the majority of surgeons performing RALP (74%, 78/106)) reported using MRI with an additional 37% (39/106) reporting the use of CT for pre-operative staging and/or planning. For surgeons performing RAPN and robot-assisted cystectomy there was more of a consensus with 97% (68/70) and 95% (54/57) of surgeons, respectively, using CT for routine preoperative imaging (Table 1).
Table 1. Which preoperative imaging modalities do you use for diagnosis and surgical planning?
| CT | MRI | USS | None | Other | |
| RALP (n = 106) | 39.8% | 73.5% | 2% | 15.1% | 8.4% |
| (39) | (78) | (3) | (16) | (9) | |
| RAPN (n = 70) | 97.1% | 42.9% | 17.1% | 0% | 2.9% |
| (68) | (30) | (12) | (0) | (2) | |
| Cystectomy (n = 57) | 94.7% | 26.3% | 1.8% | 1.8% | 5.3% |
| (54) | (15) | (1) | (1) | (3) |
Those surgeons performing RAPN were found to have the most diversity in the way they viewed pre-operative images in theater, routinely viewing images in sagittal, coronal and axial slices (Table 2). The majority of these surgeons also viewed the images as 3D reconstructions (54%, 38/70).
Table 2. How do you typically view preoperative imaging in the OR? 3D recons = three-dimensional reconstructions
| Axial slices (n) | Coronal slices (n) | Sagittal slices (n) | 3D recons. (n) | Do not view (n) | ||
| RALP (n = 106) | 49.1% | 44.3% | 31.1% | 9.4% | 31.1% | |
| (52) | (47) | (33) | (10) | (33) | ||
| RAPN (n = 70) | 68.6% | 74.3% | 60% (42) | 54.3% | 0% | |
| (48) | (52) | (38) | (0) | |||
| Cystectomy (n = 57) | 70.2% | 52.6% | 50.9% | 21.1% | 8.8% | |
| (40) | (30) | (29) | (12) | (5) |
The majority of surgeons used ultrasound intra-operatively in RAPN (51%, 35/69) with a further 25% (17/69) reporting they would use it if they had access to a ‘drop-in’ ultrasound probe (Figure 2).
Overall, 87% of respondents envisaged a role for augmented reality as a navigation tool in robotic surgery and 82% (88/107) felt that there was an additional role for the technology as a training tool.
The greatest desire for augmented reality was among those surgeons performing RAPN with 86% (54/63) feeling the technology would be of use. The largest group of surgeons felt it would be useful in identifying tumour location, with significant numbers also feeling it would be efficacious in tumor resection (Figure 3).
When enquiring about the potential for augmented reality in RALP, 79% (20/96) of respondents felt it would be of use during the procedure, with the largest group feeling it would be helpful for nerve sparing 65% (62/96) (Figure 4). The picture in cystectomy was similar with 74% (37/50) of surgeons believing augmented reality would be of use, with both nerve sparing and apical dissection highlighted as specific examples (40%, 20/50) (Figure 5). The majority also felt that it would be useful for lymph node dissection in both RALP and robot assisted cystectomy (55% (52/95) and 64% (32/50), respectively).
The results from this study suggest that the contemporary robotic surgeon views imaging as an important adjunct to operative practice. The way these images are being viewed is changing; although the majority of surgeons continue to view images as two-dimensional (2D) slices a significant minority have started to capitalize on 3D reconstructions to give them an improved appreciation of the patient’s anatomy.
This study has highlighted surgeons’ willingness to take the next step in the utilization of imaging in operative planning, augmented reality, with 87% feeling it has a role to play in robotic surgery. Although there appears to be a considerable desire for augmented reality, the technology itself is still in its infancy with the limited evidence demonstrating clinical application reporting only qualitative results [3, 7, 11, 12].
There are a number of significant issues that need to be overcome before augmented reality can be adopted in routine clinical practice. The first of these is registration (the process by which two images are positioned in the same coordinate system such that the locations of corresponding points align [13]). This process has been performed both manually and using automated algorithms with varying degrees of accuracy [2, 14]. The second issue pertains to the use of static pre-operative imaging in a dynamic operative environment; in order for the pre-operative imaging to be accurately registered it must be deformable. This problem remains as yet unresolved.
Live intra-operative imaging circumvents the problems of tissue deformation and in RAPN 51% of surgeons reported already using intra-operative ultrasound to aid in tumour resection. Cheung and colleagues [9] have published an ex vivo study highlighting the potential for intra-operative ultrasound in augmented reality partial nephrectomy. They report the overlaying of ultrasound onto the operative scene to improve the surgeon’s appreciation of the subsurface tumour anatomy, this improvement in anatomical appreciation resulted in improved resection quality over conventional ultrasound guided resection [9]. Building on this work the first in vivo use of overlaid ultrasound in RAPN has recently been reported [10]. Although good subjective feedback was received from the operating surgeon, the study was limited to a single case demonstrating feasibility and as such was not able to show an outcome benefit to the technology [10].
RAPN also appears to be the area in which augmented reality would be most readily adopted with 86% of surgeons claiming they see a use for the technology during the procedure. Within this operation there are two obvious steps to augmentation, anatomical identification (in particular vessel identification to facilitate both routine ‘full clamping’ and for the identification of secondary and tertiary vessels for ‘selective clamping’ [15]) and tumour resection. These two phases have different requirements from an augmented reality platform; the first phase of identification requires a gross overview of the anatomy without the need for high levels of registration accuracy. Tumor resection, however, necessitates almost sub-millimeter accuracy in registration and needs the system to account for the dynamic intra-operative environment. The step of anatomical identification is amenable to the use of non-deformable 3D reconstructions of pre-operative imaging while that of image-guided tumor resection is perhaps better suited to augmentation with live imaging such as ultrasound [2, 9, 16].
For RALP and robot-assisted cystectomy the steps in which surgeons felt augmented reality would be of assistance were those of neurovascular bundle preservation and apical dissection. The relative, perceived, efficacy of augmented reality in these steps correlate with previous examinations of augmented reality in RALP [17, 18]. Although surgeon preference for utilizing augmented reality while undertaking robotic prostatectomy has been demonstrated, Thompson et al. failed to demonstrate an improvement in oncological outcomes in those patients undergoing AR RALP [18].
Both nerve sparing and apical dissection require a high level of registration accuracy and a necessity for either live imaging or the deformation of pre-operative imaging to match the operative scene; achieving this level of registration accuracy is made more difficult by the mobilization of the prostate gland during the operation [17]. These problems are equally applicable to robot-assisted cystectomy. Although guidance systems have been proposed in the literature for RALP [3-5, 12, 17], none have achieved the level of accuracy required to provide assistance during nerve sparing. In addition, there are still imaging challenges that need to be overcome. Although multiparametric MRI has been shown to improve decision making in opting for a nerve sparing approach to RALP [19] the imaging is not yet able to reliably discern the exact location of the neurovascular bundle. This said, significant advances are being made with novel imaging modalities on the horizon that may allow for imaging of the neurovascular bundle in the near future [20].
The number of operations included represents a significant limitation of the study, had different index procedures been chosen different results may have been seen. This being said the index procedures selected were chosen as they represent the vast majority of uro-oncological robotic surgical practice, largely mitigating for this shortfall.
Although the available ex vivo evidence suggests that introducing augmented reality operating environments into surgical practice would help to improve outcomes [9, 21] the in vivo experience to date is limited to small volume case series reporting feasibility [2, 3, 14]. To date no study has demonstrated an in vivo outcome advantage to augmented reality guidance. In addition to this limitation augmented reality has been demonstrated to increased rates of inattention blindness among surgeons suggesting there is a trade-off between increasing visual information and the surgeon’s ability to appreciate unexpected operative events [21].
This survey shows the contemporary robotic surgeon to be comfortable with the use of imaging to aid intra-operative planning; furthermore it highlights a significant interest among the urological community in augmented reality operating platforms.
Short- to medium-term development of augmented reality systems in robotic urology surgery would be best performed using RAPN as the index procedure. Not only was this the operation where surgeons saw the greatest potential benefits, but it may also be the operation where it is most easily achievable by capitalizing on the respective benefits of technologies the surgeons are already using; pre-operative CT for anatomical identification and intra-operative ultrasound for tumour resection.
None of the authors have any conflicts of interest to declare.
| Question Asked | Question Type |
| Demographics | |
| In which country do you usually practise? | Single best answer |
| Which robotic procedures do you perform?* | Single best answer |
| Current Imaging Practice | |
| What preoperative imaging modalities do you use for the staging and surgical planning in renal cancer? | Multiple choice |
| How do you typically view preoperative imaging in theatre for renal cancer surgery? | Multiple choice |
| Do you use intraoperative ultrasound for partial nephrectomy? | Yes or No |
| What preoperative imaging modalities do you use for the staging and surgical planning in prostate cancer? | Multiple choice |
| How do you typically view preoperative imaging in theatre for prostate cancer? | Multiple choice |
| Do you use intraoperative ultrasound for robotic partial nephrectomy? | Yes or No |
| Which preoperative imaging modality do you use for staging and surgical planning in muscle invasive TCC? | Multiple choice |
| How do you typically view preoperative imaging in theatre for muscle invasive TCC? | Multiple choice |
| Do you routinely refer to preoperative imaging intraoperativley? | Yes or No |
| Do you routinely use Tilepro intraoperativley? | Yes or No |
| Augmented Reality | |
| Do you feel there is a role for augmented reality as a navigation tool in robotic surgery? | Yes or No |
| Do you feel there is a role for augmented reality as a training tool in robotic surgery? | Yes or No |
| In robotic partial nephrectomy which parts of the operation do you feel augmented reality image overlay technology would be of assistance? | Multiple choice |
| In robotic nephrectomy which parts of the operation do you feel augmented reality image overlay technology would be of assistance? | Multiple choice |
| In robotic prostatectomy which parts of the operation do you feel augmented reality image overlay technology would be of assistance? | Multiple choice |
| Would augmented reality guidance be of use in lymph node dissection in robotic prostatectomy? | Yes or No |
| In robotic cystectomy which parts of the operation do you feel augmented reality image overlay technology would be of assistance? | Multiple choice |
| Would augmented reality guidance be of use in lymph node dissection in robotic cystectomy? | Yes or No |
| *The relevant procedure related questions were displayed based on the answer to this question | |
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2. Hughes-Hallett A, Mayer EK, Marcus HJ, et al.Augmented reality partial nephrectomy: examining the current status and future perspectives. Urology 2014; 83(2): 266–273.
3. Sridhar AN, Hughes-Hallett A, Mayer EK, et al.Image-guided robotic interventions for prostate cancer. Nat Rev Urol 2013; 10(8): 452–462.
4. Cohen D, Mayer E, Chen D, et al.Eddie’ Augmented reality image guidance in minimally invasive prostatectomy. Lect Notes Comput Sci 2010; 6367: 101–110.
5. Simpfendorfer T, Baumhauer M, Muller M, et al.Augmented reality visualization during laparoscopic radical prostatectomy. J Endourol 2011; 25(12): 1841–1845.
6. Teber D, Simpfendorfer T, Guven S, et al.In vitro evaluation of a soft-tissue navigation system for laparoscopic prostatectomy. J Endourol 2010; 24(9): 1487–1491.
7. Teber D, Guven S, Simpfendörfer T, et al.Augmented reality: a new tool to improve surgical accuracy during laparoscopic partial nephrectomy? Preliminary in vitro and in vivo Eur Urol 2009; 56(2): 332–338.
8. Pratt P, Mayer E, Vale J, et al.An effective visualisation and registration system for image-guided robotic partial nephrectomy. J Robot Surg 2012; 6(1): 23–31.
9. Cheung CL, Wedlake C, Moore J, et al.Fused video and ultrasound images for minimally invasive partial nephrectomy: a phantom study. Med Image Comput Comput Assist Interv 2010; 13(Pt 3): 408–415.
10. Hughes-Hallett A, Pratt P, Mayer E, et al.Intraoperative ultrasound overlay in robot-assisted partial nephrectomy: first clinical experience. Eur Urol 2014; 65(3): 671–672.
11. Nakamura K, Naya Y, Zenbutsu S, et al.Surgical navigation using three-dimensional computed tomography images fused intraoperatively with live video. J Endourol 2010; 24(4): 521–524.
12. Ukimura O, Gill IS. Imaging-assisted endoscopic surgery: Cleveland clinic experience. J Endourol2008; 22(4):803–809.
13. Altamar HO, Ong RE, Glisson CL, et al.Kidney deformation and intraprocedural registration: a study of elements of image-guided kidney surgery. J Endourol 2011; 25(3): 511–517.
14. Nicolau S, Soler L, Mutter D, Marescaux J. Augmented reality in laparoscopic surgical oncology. Surg Oncol2011; 20(3): 189–201.
15. Ukimura O, Nakamoto M, Gill IS. Three-dimensional reconstruction of renovascular-tumor anatomy to facilitate zero-ischemia partial nephrectomy. Eur Urol2012; 61(1): 211–217.
16. Pratt P, Hughes-Hallett A, Di Marco A, et al. Multimodal reconstruction for image-guided interventions. In:Yang GZ, Darzi A (eds) Proceedings of the Hamlyn symposium on medical robotics: London. 2013; 59–61.
17. Mayer EK, Cohen D, Chen D, et al.Augmented reality image guidance in minimally invasive prostatectomy. Eur Urol Supp 2011; 10(2): 300.
18. Thompson S, Penney G, Billia M, et al.Design and evaluation of an image-guidance system for robot-assisted radical prostatectomy. BJU Int 2013; 111(7): 1081–1090.
19. Panebianco V, Salciccia S, Cattarino S, et al.Use of multiparametric MR with neurovascular bundle evaluation to optimize the oncological and functional management of patients considered for nerve-sparing radical prostatectomy. J Sex Med 2012; 9(8): 2157–2166.
20. Rai S, Srivastava A, Sooriakumaran P, Tewari A. Advances in imaging the neurovascular bundle. Curr Opin Urol2012; 22(2): 88–96.
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Posted in Frontiers in Cardiology and Cardiovascular Disorders, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, MRI, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Noninvasive Diagnostic Fractional Flow Reserve (FFR) CT on December 15, 2014| Leave a Comment »
Dynamic myocardial CT perfusion imaging for evaluation of myocardial ischemia as determined by MR imaging | DSCT.com – Your Dual-source CT experts
Reporter: Aviva Lev-Ari, PhD, RN
The aim of this study was to determine the feasibility of CT-based dynamic myocardial perfusion imaging for the assessment of myocardial ischemia and infarction compared with cardiac magnetic resonance (CMR).
Source: www.dsct.com
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It is estimated that the medical imaging market will exceed $30 billion in 2014 (FierceMedicalImaging). To put this amount in perspective; the global pharmaceutical market size for the same year is expected to be ~$1 trillion (IMS) while the global health care spending as a percentage of Gross Domestic Product (GDP) will average 10.5% globally in 2014 (Deloitte); it will reach ~$3 trillion in the USA.
Recent technology-advances, mainly miniaturization and improvement in electronic-processing components is driving increased introduction of innovative medical-imaging devices into critical nodes of major-diseases’ management pathways. Consequently, in contrast to it’s very small contribution to global health costs, medical imaging bears outstanding potential to reduce the future growth in spending on major segments in this market mainly: Drugs development and regulation (e.g. companion diagnostics and imaging surrogate markers); Disease management (e.g. non-invasive diagnosis, guided treatment and non-invasive follow-ups); and Monitoring aging-population (e.g. Imaging-based domestic sensors).
In; The Role of Medical Imaging in Personalized Medicine I discussed in length the role medical imaging assumes in drugs development. Integrating imaging into drug development processes, specifically at the early stages of drug discovery, as well as for monitoring drug delivery and the response of targeted processes to the therapy is a growing trend. A nice (and short) review highlighting the processes, opportunities, and challenges of medical imaging in new drug development is: Medical imaging in new drug clinical development.
Precise treatment is a major pillar of modern medicine. An important aspect to enable accurate administration of treatment is complementing the accurate identification of the organ location that needs to be treated with a system and methods that ensure application of treatment only, or mainly to, that location. Imaging is off-course, a major component in such composite systems. Amongst the available solution, functional-imaging modalities are gaining traction. Specifically, molecular imaging (e.g. PET, MRS) allows the visual representation, characterization, and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In oncology, it can be used to depict the abnormal molecules as well as the aberrant interactions of altered molecules on which cancers depend. Being able to detect such fundamental finger-prints of cancer is key to improved matching between drugs-based treatment and disease. Moreover, imaging-based quantified monitoring of changes in tumor metabolism and its microenvironment could provide real-time non-invasive tool to predict the evolution and progression of primary tumors, as well as the development of tumor metastases.
A recent review-paper: Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles nicely illustrates the role of imaging in treatment guidance through a comprehensive discussion of; Image-guided radiotherapeutic using intravenous nanoparticles for the delivery of localized radiation to solid cancer tumors.
One of the major limitations of current cancer therapy is the inability to deliver tumoricidal agents throughout the entire tumor mass using traditional intravenous administration. Nanoparticles carrying beta-emitting therapeutic radionuclides [DN: radioactive isotops that emits electrons as part of the decay process a list of β-emitting radionuclides used in radiotherapeutic nanoparticle preparation is given in table1 of this paper.) that are delivered using advanced image-guidance have significant potential to improve solid tumor therapy. The use of image-guidance in combination with nanoparticle carriers can improve the delivery of localized radiation to tumors. Nanoparticles labeled with certain beta-emitting radionuclides are intrinsically theranostic agents that can provide information regarding distribution and regional dosimetry within the tumor and the body. Image-guided thermal therapy results in increased uptake of intravenous nanoparticles within tumors, improving therapy. In addition, nanoparticles are ideal carriers for direct intratumoral infusion of beta-emitting radionuclides by convection enhanced delivery, permitting the delivery of localized therapeutic radiation without the requirement of the radionuclide exiting from the nanoparticle. With this approach, very high doses of radiation can be delivered to solid tumors while sparing normal organs. Recent technological developments in image-guidance, convection enhanced delivery and newly developed nanoparticles carrying beta-emitting radionuclides will be reviewed. Examples will be shown describing how this new approach has promise for the treatment of brain, head and neck, and other types of solid tumors.
Note: Drugs that have increased accumulation within the targeted site are likely to be more effective as compared with others. In that respect, Nanoparticle-based drugs have an additional advantage over free drugs with their potential to be multifunctional carriers capable of carrying both therapeutic and diagnostic imaging probes (theranostic) in the same nanocarrier. These multifunctional nanoparticles can serve as theranostic agents and facilitate personalized treatment planning.
See the example of Vintfolide in The Role of Medical Imaging in Personalized Medicine
Note: Image guided thermal ablation methods include radiofrequency (RF) ablation, microwave ablation or high intensity focused ultrasound (HIFU). Photodynamic therapy methods using external light devices to activate photosensitizing agents can also be used to treat superficial tumors or deeper tumors when used with endoscopic catheters.
For example: The use of high intensity focused ultrasound (HIFU) combined with nanoparticle therapeutics: HIFU is applied to improve drug delivery and to trigger drug release from nanoparticles. Gas-bubbles are playing the role of the drug’s nano-carrier. These are used both to increase the drug transport into the cell and as ultrasound-imaging contrast material. The ultrasound is also used for processes of drug-release and ablation.
Additional example; Multifunctional nanoparticles for tracking CED (convection enhanced delivery) distribution within tumors: Nanoparticle that could serve as a carrier not only for the therapeutic radionuclides but simultaneously also for a therapeutic drug and 4 different types of imaging contrast agents including an MRI contrast agent, PET and SPECT nuclear diagnostic imaging agents and optical contrast agents as shown below. The ability to perform multiple types of imaging on the same nanoparticles will allow studies investigating the distribution and retention of nanoparticles initially in vivo using non-invasive imaging and later at the histological level using optical imaging.
Image-guided radiotherapeutic nanoparticles have significant potential for solid tumor cancer therapy. The current success of this therapy in animals is most likely due to the improved accumulation, retention and dispersion of nanoparticles within solid tumor following image-guided therapies as well as the micro-field of the β-particle which reduces the requirement of perfectly homogeneous tumor coverage. It is also possible that the intratumoral distribution of nanoparticles may benefit from their uptake by intratumoral macrophages although more research is required to determine the importance of this aspect of intratumoral radionuclide nanoparticle therapy. This new approach to cancer therapy is a fertile ground for many new technological developments as well as for new understandings in the basic biology of cancer therapy. The clinical success of this approach will depend on progress in many areas of interdisciplinary research including imaging technology, nanoparticle technology, computer and robot assisted image-guided application of therapies, radiation physics and oncology. Close collaboration of a wide variety of scientists and physicians including chemists, nanotechnologists, drug delivery experts, radiation physicists, robotics and software experts, toxicologists, surgeons, imaging physicians, and oncologists will best facilitate the implementation of this novel approach to the treatment of cancer in the clinical environment. Image-guided nanoparticle therapies including those with β-emission radionuclide nanoparticles have excellent promise to significantly impact clinical cancer therapy and advance the field of drug delivery.
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